Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma
Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT00408005
Collaborator
(none)
1,895
215
17
8.8
Study Details
Study Description
Brief Summary
This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. After a common induction therapy, patients were risk assigned and eligible for one or both post-induction randomizations: Escalating dose Methotrexate versus High Dose Methotrexate in Interim Maintenance therapy, No Nelarabine versus Nelarabine in Consolidation therapy. T-ALL patients are risk assigned as Low Risk, Intermediate Risk or High Risk. Low Risk patients are not eligible for the Nelarabine randomization, Patients with CNS disease at diagnosis were assgined to receive High Dose Methotrexate, patients who failed induction therapy were assigned to receive Nelarabine and High Dose Methotrexate. T-LLy patients were all assigned to escalating dose Methotrexate and were risk assigned as Standard Risk, High Risk and induction failures. Standard risk patients did not receive nelarabine, High risk T-LLy patients were randomized to No Nelarabine versus Nelarabine, and Induction failures were assigned to receive Nelarabine.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
-
To determine, through randomization, the relative safety and efficacy of the addition of nelarabine (Compound 506U78) to augmented Berlin-Frankfurt-Münster (BFM) therapy (Regimen C, Children's Cancer Group [CCG]-1961).
-
To determine the relative safety and efficacy of high dose methotrexate (5 g/m^2) with leucovorin (leucovorin calcium) rescue compared to escalating methotrexate without leucovorin rescue plus pegaspargase (Capizzi I) delivered during interim maintenance.
-
To gain preliminary data on the use of nelarabine in patients with high risk T-cell lymphoblastic lymphoma and its effect on long-term survival.
SECONDARY OBJECTIVES:
- To determine the relative safety and efficacy of withholding radiation in patients with low risk T-cell acute lymphoblastic leukemia (T-ALL), while treating Intermediate and high risk patients with 1200 cGy of prophylactic cranial radiation.
OUTLINE: This is a randomized, controlled, factorial-group, multicenter study.
GROUP 0 (INDUCTION THERAPY): All patients (T-ALL and T-LLy) receive cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; duanorubicin IV on days 1, 8, 15 and 22; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease).
GROUP I ARM I COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo conformal radiation therapy (CRT). Patients with standard risk T-LLy received Arm I, and those with high risk T-LLy were randomized between Arm I and Arm II combination chemotherapy.
GROUP I ARM I COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). Standard risk T-LLy patients were assigned to Arm I and those with high risk were randomized between Arm I and Arm II.
GROUP I ARM I COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10).
Note: *Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32.
GROUP I ARM I COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL), all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).
GROUP I ARM II COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. Patients with high risk T-LLy were either randomized to Arm I or Arm II. Patients with T-LLy who failed induction therapy were assigned to Arm II.
GROUP I ARM II COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.
GROUP I ARM II COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31.
Note: *Patients with an allergy to pegaspargase receive Erwinia asparaginase on Monday, Wednesday and Friday for two consecutive weeks starting the day of asparaginase substitution.
GROUP I ARM II COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).
GROUP I ARM III COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.
GROUP I ARM III COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10).
GROUP I ARM III COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive high dose methotrexate (HDMTX) IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses.
GROUP I ARM III COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).
GROUP I ARM IV COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35.
GROUP I ARM IV COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.
GROUP I ARM IV COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive HDMTX IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses.
GROUP I ARM IV COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).
After completion of study therapy, patients are followed periodically for at least 10 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1895 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Intensified Methotrexate, Nelarabine (Compound 506U78) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-cell Acute Lymphoblastic Leukemia (ALL) or T-cell Lymphoblastic Lymphoma
Actual Study Start Date
:
Jan 22, 2007
Actual Primary Completion Date
:
Sep 30, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 0 Induction Therapy All patients (T-ALL and T-LLy) receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or PO twice daily BID on days 1-28; pegaspargase IM (may give IV over 1 to 2 hours) on day 4, 5, or 6; daunorubicin hydrochloride IV on days 1, 8, 15 and 22; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). |
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Drug: Prednisone
Given IV or PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group 1 Arm IV (Consolidation chemotherapy) Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Nelarabine
Given IV
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Radiation: Radiation Therapy
Some patients undergo testicular and/or prophylactic cranial RT
Other Names:
|
| Active Comparator: Group I Arm I (Consolidation chemotherapy) Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT. Patients with standard risk T-LLy received Arm I, and those with high risk T-LLy were randomized between Arm I and Arm II combination chemotherapy. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Leucovorin Calcium
Given PO
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Radiation: Radiation Therapy
Some patients undergo testicular and/or prophylactic cranial RT
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm I (Delayed intensification chemotherapy Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). Standard risk T-LLy patients were assigned to Arm I and those with high risk were randomized between Arm I and Arm II. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Leucovorin Calcium
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm I (Maintenance chemotherapy) Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL), all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL). |
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Prednisone
Given IV or PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm I (Interim maintenance chemotherapy) Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10). Note: *Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32. |
Drug: Leucovorin Calcium
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm II (Consolidation chemotherapy) Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. Patients with high risk T-LLy were either randomized to Arm I or Arm II. Patients with T-LLy who failed induction therapy were assigned to Arm II. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Nelarabine
Given IV
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Radiation: Radiation Therapy
Some patients undergo testicular and/or prophylactic cranial RT
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm II (Delayed intensification chemotherapy) Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Nelarabine
Given IV
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm II (Interim maintenance chemotherapy) Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Note: *Patients with an allergy to pegaspargase receive Erwinia asparaginase on Monday, Wednesday and Friday for two consecutive weeks starting the day of asparaginase substitution. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm II (Maintenance chemotherapy) Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL). |
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Nelarabine
Given IV
Other Names:
Drug: Prednisone
Given IV or PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm III (Consolidation chemotherapy) Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Leucovorin Calcium
Given PO
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Radiation: Radiation Therapy
Some patients undergo testicular and/or prophylactic cranial RT
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm III (Delayed intensification chemotherapy) Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Leucovorin Calcium
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm III (Interim maintenance chemotherapy) Patients receive HDMTX IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses. |
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given PO
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm III (Maintenance chemotherapy) Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL). |
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Prednisone
Given IV or PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm IV (Delayed intensification chemotherapy) Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age); doxorubicin IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, IV, or SC
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Nelarabine
Given IV
Other Names:
Drug: Pegaspargase
Given IM or IV
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm IV (Interim maintenance chemotherapy) Patients receive HDMTX IV over 24 hours and vincristine IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses. |
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given PO
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Group I Arm IV (Maintenance chemotherapy) Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL). |
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or PO
Other Names:
Drug: Nelarabine
Given IV
Other Names:
Drug: Prednisone
Given IV or PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) [4 years from randomization at the end of induction]
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
- Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV) [4 years from randomization at the end of induction]
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event
- Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) [4 years from randomization at the end of induction]
Disease-free survival defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, remission death) or date of last contact for those who are event-free.
- Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV) [4 years from randomization at the end of induction]
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
- Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort [4 years from end of induction]
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Secondary Outcome Measures
- Cumulative Incidence of CNS Relapse for T-ALL by Risk Group [4 years from randomization at the end of induction]
Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation.
Eligibility Criteria
Criteria
Ages Eligible for Study:
1 Year
to 30 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
T-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0434
-
Patients must have newly diagnosed T-ALL or T-lineage lymphoblastic lymphoma (T-NHL) stage II-IV; B-lineage lymphoblastic lymphoma will not be eligible for this study; a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including transmission disequilibrium test (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory
-
T-NHL PATIENTS:
-
For T-NHL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-NHL defined by the submitting institution will be accepted
-
Prior therapy restrictions
-
Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and/or IT cytarabine
-
IT chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy
-
Patients diagnosed as having T-NHL or T-ALL with respiratory distress or hyperleukocytosis may require steroids prior to the initiation of additional systemic therapy; they are eligible for AALL0434 and will be stratified, based on the initial complete blood count (CBC); steroid pretreatment may alter the risk group assessment; if the T-ALL patient's clinical status precludes a lumbar puncture within 48 hours of the initiation of steroid therapy, T-ALL patients CANNOT be classified as low risk and will be Intermediate or high risk based on the results of the day 29 marrow as above; patients with T-NHL who receive steroid pre-treatment will be classified as high risk; the dose and duration of previous steroid therapy should be carefully documented
-
For the management of airway compromise, patients who have received emergent chest irradiation up to 600 cGy will be eligible for this study
-
Patients with a prior seizure disorder requiring anti-convulsant therapy are not eligible to receive nelarabine; in addition, patients with pre-existing grade 2 (or greater) peripheral neurotoxicity, as determined prior to Induction treatment by the treating physician or a neurologist, are not eligible to receive nelarabine; these restrictions in eligibility are designed to prevent excessive nelarabine-induced central and peripheral neurotoxicity in at-risk patients; for the purposes of this study, this includes any patient that has received anticonvulsant therapy to prevent/treat seizures in the prior two years
Exclusion Criteria:
-
Pregnant or lactating females are ineligible
-
Patients with Down syndrome are ineligible to enroll onto this study
-
For T-NHL patients the following additional exclusion criteria apply:
-
B-precursor lymphoblastic lymphoma
-
Morphologically unclassifiable lymphoma
-
Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma
-
CNS3-positive or testicular involvement
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Alabama | Birmingham | Alabama | United States | 35233 |
| 2 | University of Alabama at Birmingham Cancer Center | Birmingham | Alabama | United States | 35233 |
| 3 | USA Health Strada Patient Care Center | Mobile | Alabama | United States | 36604 |
| 4 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
| 5 | Banner University Medical Center - Tucson | Tucson | Arizona | United States | 85719 |
| 6 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202-3591 |
| 7 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 8 | Kaiser Permanente Downey Medical Center | Downey | California | United States | 90242 |
| 9 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 10 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
| 11 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
| 12 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 13 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 14 | Valley Children's Hospital | Madera | California | United States | 93636 |
| 15 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
| 16 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
| 17 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
| 18 | Lucile Packard Children's Hospital Stanford University | Palo Alto | California | United States | 94304 |
| 19 | Sutter Medical Center Sacramento | Sacramento | California | United States | 95816 |
| 20 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 21 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
| 22 | UCSF Medical Center-Parnassus | San Francisco | California | United States | 94143 |
| 23 | UCSF Medical Center-Mission Bay | San Francisco | California | United States | 94158 |
| 24 | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance | California | United States | 90502 |
| 25 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 26 | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | United States | 80218 |
| 27 | Connecticut Children's Medical Center | Hartford | Connecticut | United States | 06106 |
| 28 | Yale University | New Haven | Connecticut | United States | 06520 |
| 29 | Alfred I duPont Hospital for Children | Wilmington | Delaware | United States | 19803 |
| 30 | MedStar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
| 31 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 32 | Broward Health Medical Center | Fort Lauderdale | Florida | United States | 33316 |
| 33 | Lee Memorial Health System | Fort Myers | Florida | United States | 33901 |
| 34 | Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | United States | 33908 |
| 35 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
| 36 | Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
| 37 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
| 38 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
| 39 | Nicklaus Children's Hospital | Miami | Florida | United States | 33155 |
| 40 | Miami Cancer Institute | Miami | Florida | United States | 33176 |
| 41 | AdventHealth Orlando | Orlando | Florida | United States | 32803 |
| 42 | Arnold Palmer Hospital for Children | Orlando | Florida | United States | 32806 |
| 43 | Nemours Children's Clinic - Orlando | Orlando | Florida | United States | 32806 |
| 44 | Orlando Health Cancer Institute | Orlando | Florida | United States | 32806 |
| 45 | Nemours Children's Hospital | Orlando | Florida | United States | 32827 |
| 46 | Nemours Children's Clinic - Pensacola | Pensacola | Florida | United States | 32504 |
| 47 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
| 48 | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | United States | 33607 |
| 49 | Saint Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
| 50 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
| 51 | Augusta University Medical Center | Augusta | Georgia | United States | 30912 |
| 52 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
| 53 | University of Hawaii Cancer Center | Honolulu | Hawaii | United States | 96813 |
| 54 | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | United States | 96826 |
| 55 | Tripler Army Medical Center | Honolulu | Hawaii | United States | 96859 |
| 56 | Saint Luke's Cancer Institute - Boise | Boise | Idaho | United States | 83712 |
| 57 | Lurie Children's Hospital-Chicago | Chicago | Illinois | United States | 60611 |
| 58 | University of Illinois | Chicago | Illinois | United States | 60612 |
| 59 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
| 60 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 61 | Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | United States | 60453 |
| 62 | Advocate Children's Hospital-Park Ridge | Park Ridge | Illinois | United States | 60068 |
| 63 | Advocate Lutheran General Hospital | Park Ridge | Illinois | United States | 60068 |
| 64 | Saint Jude Midwest Affiliate | Peoria | Illinois | United States | 61637 |
| 65 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 66 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
| 67 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
| 68 | Blank Children's Hospital | Des Moines | Iowa | United States | 50309 |
| 69 | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
| 70 | University of Kansas Cancer Center | Kansas City | Kansas | United States | 66160 |
| 71 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
| 72 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
| 73 | Tulane University Health Sciences Center | New Orleans | Louisiana | United States | 70112 |
| 74 | Children's Hospital New Orleans | New Orleans | Louisiana | United States | 70118 |
| 75 | Ochsner Medical Center Jefferson | New Orleans | Louisiana | United States | 70121 |
| 76 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
| 77 | Maine Children's Cancer Program | Scarborough | Maine | United States | 04074 |
| 78 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
| 79 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
| 80 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 81 | Walter Reed National Military Medical Center | Bethesda | Maryland | United States | 20889-5600 |
| 82 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 83 | Baystate Medical Center | Springfield | Massachusetts | United States | 01199 |
| 84 | UMass Memorial Medical Center - University Campus | Worcester | Massachusetts | United States | 01655 |
| 85 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
| 86 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 87 | Ascension Saint John Hospital | Detroit | Michigan | United States | 48236 |
| 88 | Michigan State University Clinical Center | East Lansing | Michigan | United States | 48824-7016 |
| 89 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
| 90 | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | United States | 49503 |
| 91 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
| 92 | Kalamazoo Center for Medical Studies | Kalamazoo | Michigan | United States | 49008 |
| 93 | Beaumont Children's Hospital-Royal Oak | Royal Oak | Michigan | United States | 48073 |
| 94 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
| 95 | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
| 96 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 97 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
| 98 | Columbia Regional | Columbia | Missouri | United States | 65201 |
| 99 | Children's Mercy Hospitals and Clinics | Kansas City | Missouri | United States | 64108 |
| 100 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 101 | Mercy Hospital Saint Louis | Saint Louis | Missouri | United States | 63141 |
| 102 | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | United States | 68114 |
| 103 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 104 | Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada | United States | 89135 |
| 105 | Summerlin Hospital Medical Center | Las Vegas | Nevada | United States | 89144 |
| 106 | Nevada Cancer Research Foundation NCORP | Las Vegas | Nevada | United States | 89169 |
| 107 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 108 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 109 | Saint Barnabas Medical Center | Livingston | New Jersey | United States | 07039 |
| 110 | Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
| 111 | Saint Peter's University Hospital | New Brunswick | New Jersey | United States | 08901 |
| 112 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
| 113 | Newark Beth Israel Medical Center | Newark | New Jersey | United States | 07112 |
| 114 | Saint Joseph's Regional Medical Center | Paterson | New Jersey | United States | 07503 |
| 115 | Overlook Hospital | Summit | New Jersey | United States | 07902 |
| 116 | University of New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87102 |
| 117 | Albany Medical Center | Albany | New York | United States | 12208 |
| 118 | Montefiore Medical Center - Moses Campus | Bronx | New York | United States | 10467 |
| 119 | Brooklyn Hospital Center | Brooklyn | New York | United States | 11201 |
| 120 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 121 | NYU Winthrop Hospital | Mineola | New York | United States | 11501 |
| 122 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
| 123 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
| 124 | Mount Sinai Hospital | New York | New York | United States | 10029 |
| 125 | NYP/Weill Cornell Medical Center | New York | New York | United States | 10065 |
| 126 | University of Rochester | Rochester | New York | United States | 14642 |
| 127 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
| 128 | New York Medical College | Valhalla | New York | United States | 10595 |
| 129 | Mission Hospital | Asheville | North Carolina | United States | 28801 |
| 130 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
| 131 | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | United States | 28203 |
| 132 | Novant Health Presbyterian Medical Center | Charlotte | North Carolina | United States | 28204 |
| 133 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 134 | East Carolina University | Greenville | North Carolina | United States | 27834 |
| 135 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 136 | Sanford Broadway Medical Center | Fargo | North Dakota | United States | 58122 |
| 137 | Children's Hospital Medical Center of Akron | Akron | Ohio | United States | 44308 |
| 138 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 139 | Rainbow Babies and Childrens Hospital | Cleveland | Ohio | United States | 44106 |
| 140 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 141 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 142 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
| 143 | ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital | Toledo | Ohio | United States | 43606 |
| 144 | Mercy Children's Hospital | Toledo | Ohio | United States | 43608 |
| 145 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 146 | Natalie Warren Bryant Cancer Center at Saint Francis | Tulsa | Oklahoma | United States | 74136 |
| 147 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
| 148 | Legacy Emanuel Hospital and Health Center | Portland | Oregon | United States | 97227 |
| 149 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 150 | Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | United States | 18017 |
| 151 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
| 152 | Penn State Children's Hospital | Hershey | Pennsylvania | United States | 17033 |
| 153 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 154 | Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania | United States | 19134 |
| 155 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
| 156 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 157 | Prisma Health Richland Hospital | Columbia | South Carolina | United States | 29203 |
| 158 | BI-LO Charities Children's Cancer Center | Greenville | South Carolina | United States | 29605 |
| 159 | Greenville Cancer Treatment Center | Greenville | South Carolina | United States | 29605 |
| 160 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
| 161 | T C Thompson Children's Hospital | Chattanooga | Tennessee | United States | 37403 |
| 162 | East Tennessee Childrens Hospital | Knoxville | Tennessee | United States | 37916 |
| 163 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 164 | Texas Tech University Health Sciences Center-Amarillo | Amarillo | Texas | United States | 79106 |
| 165 | Dell Children's Medical Center of Central Texas | Austin | Texas | United States | 78723 |
| 166 | Driscoll Children's Hospital | Corpus Christi | Texas | United States | 78411 |
| 167 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 168 | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | United States | 75390 |
| 169 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 170 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
| 171 | Covenant Children's Hospital | Lubbock | Texas | United States | 79410 |
| 172 | Children's Hospital of San Antonio | San Antonio | Texas | United States | 78207 |
| 173 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
| 174 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
| 175 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
| 176 | Primary Children's Hospital | Salt Lake City | Utah | United States | 84113 |
| 177 | University of Vermont and State Agricultural College | Burlington | Vermont | United States | 05405 |
| 178 | University of Virginia Cancer Center | Charlottesville | Virginia | United States | 22908 |
| 179 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22042 |
| 180 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
| 181 | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | United States | 23298 |
| 182 | Carilion Children's | Roanoke | Virginia | United States | 24014 |
| 183 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 184 | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | United States | 99204 |
| 185 | Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | United States | 98405 |
| 186 | Madigan Army Medical Center | Tacoma | Washington | United States | 98431 |
| 187 | West Virginia University Charleston Division | Charleston | West Virginia | United States | 25304 |
| 188 | Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin | United States | 54301 |
| 189 | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin | United States | 53792 |
| 190 | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin | United States | 54449 |
| 191 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 192 | Royal Brisbane and Women's Hospital | Herston | Queensland | Australia | 4029 |
| 193 | Royal Children's Hospital-Brisbane | Herston | Queensland | Australia | 4029 |
| 194 | Queensland Children's Hospital | South Brisbane | Queensland | Australia | 4101 |
| 195 | Women's and Children's Hospital-Adelaide | North Adelaide | South Australia | Australia | 5006 |
| 196 | Monash Medical Center-Clayton Campus | Clayton | Victoria | Australia | 3168 |
| 197 | Royal Children's Hospital | Parkville | Victoria | Australia | 3052 |
| 198 | Princess Margaret Hospital for Children | Perth | Western Australia | Australia | 6008 |
| 199 | Alberta Children's Hospital | Calgary | Alberta | Canada | T3B 6A8 |
| 200 | University of Alberta Hospital | Edmonton | Alberta | Canada | T6G 2B7 |
| 201 | British Columbia Children's Hospital | Vancouver | British Columbia | Canada | V6H 3V4 |
| 202 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 203 | Janeway Child Health Centre | Saint John's | Newfoundland and Labrador | Canada | A1B 3V6 |
| 204 | IWK Health Centre | Halifax | Nova Scotia | Canada | B3K 6R8 |
| 205 | Kingston Health Sciences Centre | Kingston | Ontario | Canada | K7L 2V7 |
| 206 | Children's Hospital | London | Ontario | Canada | N6A 5W9 |
| 207 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
| 208 | Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
| 209 | The Montreal Children's Hospital of the MUHC | Montreal | Quebec | Canada | H3H 1P3 |
| 210 | Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7T1 |
| 211 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
| 212 | Starship Children's Hospital | Grafton | Auckland | New Zealand | 1145 |
| 213 | Christchurch Hospital | Christchurch | New Zealand | 8011 | |
| 214 | Swiss Pediatric Oncology Group - Geneva | Geneva | Switzerland | 1205 | |
| 215 | Swiss Pediatric Oncology Group - Lausanne | Lausanne | Switzerland | 1011 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Stuart S Winter, Children's Oncology Group
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00408005
Other Study ID Numbers:
- NCI-2009-00307
- NCI-2009-00307
- COG-AALL0434
- 07-169
- CDR0000514500
- AALL0434
- AALL0434
- U10CA098543
- U10CA180886
First Posted:
Dec 5, 2006
Last Update Posted:
Jul 28, 2022
Last Verified:
Mar 1, 2022
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Patients were stratified between the 2 disease groups (T-ALL and T-LLy) for Induction and then risk assigned treatment based upon the patient's response. |
| Arm/Group Title | T-ALL Induction Therapy | T-LLy Induction Therapy | T-ALL: Capizzi MTX Without Nelarabine | T-ALL: Capizzi MTX With Nelarabine | T-ALL: High Dose MTX Without Nelarabine | T-ALL: High Dose MTX With Nelarabine | T-LLy: Capizzi MTX Without Nelarabine | T-LLy: Capizzi MTX With Nelarabine |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | All patients diagnosed as T-ALL for induction | All patients diagnosed as T-LLy for induction | T-All patients who received Capizzi MTX without Nelarabine | T-All patients who received Capizzi MTX with Nelarabine | T-All patients who received High Dose MTX without Nelarabine | T-All patients who received High Dose MTX with Nelarabine | T-LLy patients who received Capizzi MTX without Nelarabine | T-LLy patients who received Capizzi MTX with Nelarabine |
| Period Title: Induction | ||||||||
| STARTED | 1596 | 299 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 1189 | 205 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 407 | 94 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Induction | ||||||||
| STARTED | 0 | 0 | 372 | 147 | 451 | 219 | 143 | 62 |
| Low Risk | 0 | 0 | 217 | 0 | 55 | 0 | 0 | 0 |
| Intermediate Risk | 0 | 0 | 99 | 95 | 257 | 93 | 0 | 0 |
| High Risk | 0 | 0 | 56 | 52 | 55 | 52 | 0 | 0 |
| CNS 3 and/or Testicular Disease | 0 | 0 | 0 | 0 | 84 | 31 | 0 | 0 |
| T-ALL M3 Marrow End of Induction | 0 | 0 | 0 | 0 | 0 | 43 | 0 | 0 |
| T-LLy Standard Risk | 0 | 0 | 0 | 0 | 0 | 0 | 82 | 0 |
| T-LLy High Risk | 0 | 0 | 0 | 0 | 0 | 0 | 61 | 60 |
| T-LLy Induction Failure | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| COMPLETED | 0 | 0 | 287 | 103 | 319 | 118 | 115 | 48 |
| NOT COMPLETED | 0 | 0 | 85 | 44 | 132 | 101 | 28 | 14 |
Baseline Characteristics
| Arm/Group Title | T-ALL Induction Therapy | T-LLy Induction Therapy | Total |
|---|---|---|---|
| Arm/Group Description | All patients diagnosed as T-ALL for induction | All patients diagnosed as T-LLy for induction | Total of all reporting groups |
| Overall Participants | 1596 | 299 | 1895 |
| Age (Count of Participants) | |||
| <=18 years |
1493
93.5%
|
268
89.6%
|
1761
92.9%
|
| Between 18 and 65 years |
103
6.5%
|
31
10.4%
|
134
7.1%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
10.05
(5.3)
|
11.13
(5.8)
|
10.22
(5.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
407
25.5%
|
90
30.1%
|
497
26.2%
|
| Male |
1189
74.5%
|
209
69.9%
|
1398
73.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
227
14.2%
|
45
15.1%
|
272
14.4%
|
| Not Hispanic or Latino |
1307
81.9%
|
244
81.6%
|
1551
81.8%
|
| Unknown or Not Reported |
62
3.9%
|
10
3.3%
|
72
3.8%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
6
0.4%
|
1
0.3%
|
7
0.4%
|
| Asian |
87
5.5%
|
11
3.7%
|
98
5.2%
|
| Native Hawaiian or Other Pacific Islander |
12
0.8%
|
4
1.3%
|
16
0.8%
|
| Black or African American |
204
12.8%
|
50
16.7%
|
254
13.4%
|
| White |
1122
70.3%
|
208
69.6%
|
1330
70.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
165
10.3%
|
25
8.4%
|
190
10%
|
Outcome Measures
| Title | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) |
|---|---|
| Description | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. |
| Time Frame | 4 years from randomization at the end of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Includes only T-cell Acute Lymphoblastic Leukemia (T-ALL) patients randomized to Nelarabine versus No Nelarabine. T-LLY patients are excluded from this analysis. Induction failures non-randomly assigned to Arm IV were excluded from this analysis. |
| Arm/Group Title | ARM I (Combination Chemotherapy) | ARM II (Combination Chemotherapy) | ARM III (Combination Chemotherapy) | ARM IV (Combination Chemotherapy) |
|---|---|---|---|---|
| Arm/Group Description | No Nelarabine, Capizzi Methotrexate | Nelarabine, Capizzi Methotrexate | No Nelarabine, High-Dose Methotrexate | Nelarabine, High-Dose Methotrexate |
| Measure Participants | 151 | 147 | 185 | 176 |
| Number (95% Confidence Interval) [percent probability] |
89.01
|
90.53
|
78.07
|
86.46
|
| Title | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV) |
|---|---|
| Description | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event |
| Time Frame | 4 years from randomization at the end of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Includes subjects randomized to Nelarabine versus No Nelarabine |
| Arm/Group Title | ARM I and ARM III (Combination Chemotherapy) | ARM II and ARM IV (Combination Chemotherapy) |
|---|---|---|
| Arm/Group Description | No Nelarabine (Combined) | Nelarabine (Combined) |
| Measure Participants | 336 | 323 |
| Number (95% Confidence Interval) [percent probability] |
82.96
|
88.30
|
| Title | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) |
|---|---|
| Description | Disease-free survival defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, remission death) or date of last contact for those who are event-free. |
| Time Frame | 4 years from randomization at the end of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Includes only T-cell Acute Lymphoblastic Leukemia (T-ALL) patients randomized to Capizzi Methotrexate (CMTX) versus High-Dose Methotrexate (HDMTX). CNS3 patients non-randomly assigned to HDMTX (Arms III and IV) and Induction failures non-randomly assigned to Arm IV were excluded. T-LLY patients are excluded. |
| Arm/Group Title | ARM I (Combination Chemotherapy) | ARM II (Combination Chemotherapy) | ARM III (Combination Chemotherapy) | ARM IV (Combination Chemotherapy) |
|---|---|---|---|---|
| Arm/Group Description | No Nelarabine, Capizzi Methotrexate | Nelarabine, Capizzi Methotrexate | No Nelarabine, High-Dose Methotrexate | Nelarabine, High-Dose Methotrexate |
| Measure Participants | 372 | 147 | 367 | 145 |
| Number (95% Confidence Interval) [percent probability] |
91.76
|
90.53
|
86.06
|
84.89
|
| Title | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV) |
|---|---|
| Description | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. |
| Time Frame | 4 years from randomization at the end of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Includes subjects randomized to Capizzi Methotrexate versus High-Dose Methotrexate |
| Arm/Group Title | ARM I and ARM II (Combination Chemotherapy) | ARM III and ARM IV (Combination Chemotherapy) |
|---|---|---|
| Arm/Group Description | Capizzi Methotrexate (Combined) | High-Dose Methotrexate (Combined) |
| Measure Participants | 519 | 512 |
| Number (95% Confidence Interval) [percent probability] |
91.45
|
85.78
|
| Title | Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort |
|---|---|
| Description | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. |
| Time Frame | 4 years from end of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Includes T-cell lymphoblastic lymphoma (T-LLy) patients that are standard risk, high risk and induction failures. All Standard risk T-LLy patients only received Arm I. Induction failures were assigned to Arm II. |
| Arm/Group Title | ARM I (Combination Chemotherapy) | ARM II (Combination Chemotherapy) |
|---|---|---|
| Arm/Group Description | No Nelarabine, Capizzi Methotrexate | Nelarabine, Capizzi Methotrexate |
| Measure Participants | 143 | 62 |
| Standard Risk |
87.4
|
|
| High Risk |
85.1
|
85.0
|
| Induction Failure |
100
|
| Title | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group |
|---|---|
| Description | Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation. |
| Time Frame | 4 years from randomization at the end of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Includes only low risk, intermediate risk and high risk T-cell Acute Lymphoblastic Leukemia (T-ALL) subjects. There were no low risk participants on Arm II and Arm IV. Patients with CNS3, and Induction Failures are excluded from this analysis. |
| Arm/Group Title | ARM I (Combination Chemotherapy) | ARM II (Combination Chemotherapy) | ARM III (Combination Chemotherapy) | ARM IV (Combination Chemotherapy) |
|---|---|---|---|---|
| Arm/Group Description | No Nelarabine, Capizzi Methotrexate | Nelarabine, Capizzi Methotrexate | No Nelarabine, High-Dose Methotrexate | Nelarabine, High-Dose Methotrexate |
| Measure Participants | 372 | 147 | 451 | 176 |
| Low Risk |
1.85
|
1.92
|
||
| Intermediate Risk |
1.16
|
1.08
|
9.1
|
0.85
|
| High Risk |
3.64
|
0
|
6.52
|
3.45
|
Adverse Events
| Time Frame | From start of Induction therapy to end of Maintenance therapy, up to 10 years | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events. | |||||||||||||||||||
| Arm/Group Title | T-ALL Induction Therapy | T-ALL Post Induction Therapy | T-ALL: Capizzi MTX Without Nelarabine | T-ALL: Capizzi MTX With Nelarabine | T-ALL: High Dose MTX Without Nelarabine | T-ALL: High Dose MTX With Nelarabine | T-LLy Induction Therapy | T-LLy Post Induction Therapy | T-LLy: Capizzi MTX Without Nelarabine | T-LLy: Capizzi MTX With Nelarabine | ||||||||||
| Arm/Group Description | All patients diagnosed as T-ALL for induction | T-ALL patients who went off therapy at the end of induction, excluding patients who died at induction | T-All patients who received Capizzi MTX without Nelarabine | T-All patients who received Capizzi MTX with Nelarabine | T-All patients who received High Dose MTX without Nelarabine | T-All patients who received High Dose MTX with Nelarabine | All patients diagnosed as T-LLy for induction | T-LLy patients who went off therapy at the end of induction, excluding patients who died at induction | T-LLy patients who received Capizzi MTX without Nelarabine | T-LLy patients who received Capizzi MTX with Nelarabine | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| T-ALL Induction Therapy | T-ALL Post Induction Therapy | T-ALL: Capizzi MTX Without Nelarabine | T-ALL: Capizzi MTX With Nelarabine | T-ALL: High Dose MTX Without Nelarabine | T-ALL: High Dose MTX With Nelarabine | T-LLy Induction Therapy | T-LLy Post Induction Therapy | T-LLy: Capizzi MTX Without Nelarabine | T-LLy: Capizzi MTX With Nelarabine | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/1563 (0.4%) | 39/368 (10.6%) | 26/372 (7%) | 10/147 (6.8%) | 45/451 (10%) | 35/219 (16%) | 0/285 (0%) | 8/80 (10%) | 17/143 (11.9%) | 5/62 (8.1%) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| T-ALL Induction Therapy | T-ALL Post Induction Therapy | T-ALL: Capizzi MTX Without Nelarabine | T-ALL: Capizzi MTX With Nelarabine | T-ALL: High Dose MTX Without Nelarabine | T-ALL: High Dose MTX With Nelarabine | T-LLy Induction Therapy | T-LLy Post Induction Therapy | T-LLy: Capizzi MTX Without Nelarabine | T-LLy: Capizzi MTX With Nelarabine | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 25/1563 (1.6%) | 1/368 (0.3%) | 18/372 (4.8%) | 44/147 (29.9%) | 23/451 (5.1%) | 66/219 (30.1%) | 1/285 (0.4%) | 0/80 (0%) | 10/143 (7%) | 20/62 (32.3%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anemia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Blood and lymphatic system disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Disseminated intravascular coagulation | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Febrile neutropenia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 2 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Leukocytosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Cardiac disorders | ||||||||||||||||||||
| Atrial fibrillation | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Left ventricular systolic dysfunction | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pericardial effusion | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Sinus tachycardia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||
| Blurred vision | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Optic nerve disorder | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal distension | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Abdominal pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 4/219 (1.8%) | 5 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Ascites | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Colitis | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Constipation | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dysphagia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Gastrointestinal disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Ileal perforation | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Intra-abdominal hemorrhage | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Mucositis oral | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Nausea | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Oral pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pancreatic necrosis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pancreatitis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 1/451 (0.2%) | 1 | 5/219 (2.3%) | 5 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 1/62 (1.6%) | 1 |
| Rectal ulcer | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Typhlitis | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Upper gastrointestinal hemorrhage | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vomiting | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| General disorders | ||||||||||||||||||||
| Death NOS | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Facial pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Fatigue | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Fever | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 3/147 (2%) | 3 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| General disorders and administration site conditions - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Multi-organ failure | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Hepatobiliary disorders | ||||||||||||||||||||
| Hepatic failure | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hepatobiliary disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Portal hypertension | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||
| Allergic reaction | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 1/451 (0.2%) | 1 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 2/62 (3.2%) | 2 |
| Anaphylaxis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 5/147 (3.4%) | 5 | 2/451 (0.4%) | 2 | 8/219 (3.7%) | 8 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 3/62 (4.8%) | 3 |
| Immune system disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||
| Appendicitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Catheter related infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Enterocolitis infectious | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Infections and infestations - Other, specify | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 2/147 (1.4%) | 2 | 4/451 (0.9%) | 4 | 6/219 (2.7%) | 7 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Lung infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Meningitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Sepsis | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 6/147 (4.1%) | 7 | 2/451 (0.4%) | 2 | 6/219 (2.7%) | 8 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 2 | 2/62 (3.2%) | 2 |
| Skin infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Tooth infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Upper respiratory infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Venous injury | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Investigations | ||||||||||||||||||||
| Alanine aminotransferase increased | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 5/147 (3.4%) | 5 | 0/451 (0%) | 0 | 8/219 (3.7%) | 8 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 2/62 (3.2%) | 2 |
| Alkaline phosphatase increased | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Aspartate aminotransferase increased | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 3/147 (2%) | 3 | 0/451 (0%) | 0 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Blood bilirubin increased | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 2 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| CPK increased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Creatinine increased | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Fibrinogen decreased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| GGT increased | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| INR increased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Investigations - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Lipase increased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 3/147 (2%) | 3 | 0/451 (0%) | 0 | 7/219 (3.2%) | 7 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Lymphocyte count decreased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Neutrophil count decreased | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Platelet count decreased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Serum amylase increased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Weight loss | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| White blood cell decreased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Acidosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Anorexia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dehydration | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Glucose intolerance | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hyperglycemia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Hyperkalemia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypernatremia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypertriglyceridemia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Hyperuricemia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypoalbuminemia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Hypocalcemia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypoglycemia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypokalemia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 3/147 (2%) | 3 | 1/451 (0.2%) | 1 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hyponatremia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypophosphatemia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Tumor lysis syndrome | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Arthralgia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Avascular necrosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Back pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Generalized muscle weakness | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Joint effusion | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Muscle weakness left-sided | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Muscle weakness lower limb | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Musculoskeletal and connective tissue disorder - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 3/147 (2%) | 3 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Myalgia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Myositis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pain in extremity | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Leukemia secondary to oncology chemotherapy | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Treatment related secondary malignancy | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||
| Arachnoiditis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Ataxia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Depressed level of consciousness | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dysarthria | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dysphasia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Edema cerebral | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Encephalopathy | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 2 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Extrapyramidal disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Facial muscle weakness | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Facial nerve disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Glossopharyngeal nerve disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Headache | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypersomnia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypoglossal nerve disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Intracranial hemorrhage | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Ischemia cerebrovascular | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Leukoencephalopathy | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 2/62 (3.2%) | 2 |
| Memory impairment | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Movements involuntary | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Nervous system disorders - Other, specify | 1/1563 (0.1%) | 3 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Neuralgia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Paresthesia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Peripheral motor neuropathy | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 3/147 (2%) | 4 | 0/451 (0%) | 0 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Peripheral sensory neuropathy | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 3/147 (2%) | 3 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Recurrent laryngeal nerve palsy | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Reversible posterior leukoencephalopathy syndrome | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Seizure | 2/1563 (0.1%) | 2 | 1/368 (0.3%) | 1 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 4/62 (6.5%) | 5 |
| Stroke | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Syncope | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Transient ischemic attacks | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||||||
| Pregnancy, puerperium and perinatal conditions - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Psychiatric disorders | ||||||||||||||||||||
| Agitation | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Anxiety | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Confusion | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Delirium | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Depression | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Insomnia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Suicidal ideation | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||
| Acute kidney injury | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Cystitis noninfective | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hematuria | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Renal and urinary disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Renal calculi | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Renal colic | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urinary frequency | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Adult respiratory distress syndrome | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Bronchopulmonary hemorrhage | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dyspnea | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Epistaxis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypoxia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Pleural effusion | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pneumonitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pulmonary edema | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Respiratory failure | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Sore throat | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Wheezing | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Rash maculo-papular | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urticaria | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||
| Capillary leak syndrome | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hematoma | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypertension | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypotension | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 3/147 (2%) | 3 | 2/451 (0.4%) | 2 | 6/219 (2.7%) | 9 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Thromboembolic event | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vascular disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| T-ALL Induction Therapy | T-ALL Post Induction Therapy | T-ALL: Capizzi MTX Without Nelarabine | T-ALL: Capizzi MTX With Nelarabine | T-ALL: High Dose MTX Without Nelarabine | T-ALL: High Dose MTX With Nelarabine | T-LLy Induction Therapy | T-LLy Post Induction Therapy | T-LLy: Capizzi MTX Without Nelarabine | T-LLy: Capizzi MTX With Nelarabine | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 983/1563 (62.9%) | 0/368 (0%) | 357/372 (96%) | 134/147 (91.2%) | 436/451 (96.7%) | 197/219 (90%) | 152/285 (53.3%) | 4/80 (5%) | 140/143 (97.9%) | 55/62 (88.7%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anemia | 57/1563 (3.6%) | 60 | 0/368 (0%) | 0 | 87/372 (23.4%) | 139 | 26/147 (17.7%) | 37 | 93/451 (20.6%) | 142 | 25/219 (11.4%) | 29 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 23/143 (16.1%) | 33 | 9/62 (14.5%) | 12 |
| Blood and lymphatic system disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 5 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 1/80 (1.3%) | 1 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Bone marrow hypocellular | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Disseminated intravascular coagulation | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Febrile neutropenia | 96/1563 (6.1%) | 101 | 0/368 (0%) | 0 | 233/372 (62.6%) | 504 | 87/147 (59.2%) | 153 | 283/451 (62.7%) | 614 | 102/219 (46.6%) | 168 | 3/285 (1.1%) | 3 | 2/80 (2.5%) | 2 | 91/143 (63.6%) | 160 | 27/62 (43.5%) | 52 |
| Hemolysis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hemolytic uremic syndrome | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Leukocytosis | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||
| Asystole | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Cardiac disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Chest pain - cardiac | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Left ventricular systolic dysfunction | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Pericardial effusion | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pericardial tamponade | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Sinus bradycardia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Sinus tachycardia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 3 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Supraventricular tachycardia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Ventricular tachycardia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||
| Ear pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hearing impaired | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Middle ear inflammation | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Tinnitus | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||||||
| Adrenal insufficiency | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Cushingoid | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypothyroidism | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||
| Blurred vision | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Conjunctivitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Extraocular muscle paresis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Eye disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Eyelid function disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Night blindness | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Optic nerve disorder | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Papilledema | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Photophobia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vitreous hemorrhage | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal distension | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Abdominal pain | 22/1563 (1.4%) | 22 | 0/368 (0%) | 0 | 28/372 (7.5%) | 34 | 8/147 (5.4%) | 13 | 19/451 (4.2%) | 30 | 13/219 (5.9%) | 15 | 3/285 (1.1%) | 3 | 0/80 (0%) | 0 | 6/143 (4.2%) | 7 | 4/62 (6.5%) | 6 |
| Anal mucositis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 5/372 (1.3%) | 5 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Anal pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Ascites | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Colitis | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 2/147 (1.4%) | 2 | 9/451 (2%) | 9 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 7/143 (4.9%) | 7 | 1/62 (1.6%) | 3 |
| Colonic perforation | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Constipation | 18/1563 (1.2%) | 18 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 4/219 (1.8%) | 4 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 2/62 (3.2%) | 3 |
| Dental caries | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Diarrhea | 14/1563 (0.9%) | 14 | 0/368 (0%) | 0 | 20/372 (5.4%) | 21 | 7/147 (4.8%) | 7 | 26/451 (5.8%) | 27 | 8/219 (3.7%) | 8 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 2/62 (3.2%) | 6 |
| Duodenal obstruction | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dyspepsia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dysphagia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Enterocolitis | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Esophageal pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Esophagitis | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Gastritis | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 1/62 (1.6%) | 1 |
| Gastroesophageal reflux disease | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Gastrointestinal disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 2/219 (0.9%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 3 | 0/62 (0%) | 0 |
| Gastroparesis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Gingival pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hemorrhoidal hemorrhage | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hemorrhoids | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Ileus | 10/1563 (0.6%) | 10 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 3/451 (0.7%) | 4 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Intra-abdominal hemorrhage | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Lip pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Mucositis oral | 17/1563 (1.1%) | 17 | 0/368 (0%) | 0 | 54/372 (14.5%) | 64 | 19/147 (12.9%) | 21 | 77/451 (17.1%) | 83 | 35/219 (16%) | 37 | 3/285 (1.1%) | 3 | 0/80 (0%) | 0 | 24/143 (16.8%) | 28 | 9/62 (14.5%) | 10 |
| Nausea | 9/1563 (0.6%) | 9 | 0/368 (0%) | 0 | 32/372 (8.6%) | 37 | 14/147 (9.5%) | 18 | 20/451 (4.4%) | 25 | 17/219 (7.8%) | 18 | 5/285 (1.8%) | 5 | 0/80 (0%) | 0 | 13/143 (9.1%) | 15 | 6/62 (9.7%) | 9 |
| Oral hemorrhage | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Oral pain | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 10/372 (2.7%) | 12 | 1/147 (0.7%) | 1 | 9/451 (2%) | 9 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Pancreatic duct stenosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pancreatic fistula | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pancreatic hemorrhage | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pancreatic necrosis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pancreatitis | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 9/372 (2.4%) | 9 | 10/147 (6.8%) | 13 | 15/451 (3.3%) | 19 | 8/219 (3.7%) | 8 | 1/285 (0.4%) | 1 | 2/80 (2.5%) | 2 | 9/143 (6.3%) | 9 | 1/62 (1.6%) | 1 |
| Proctitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Rectal fistula | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Rectal mucositis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Rectal pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 3/372 (0.8%) | 5 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Small intestinal mucositis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Stomach pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Toothache | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Typhlitis | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 12/372 (3.2%) | 13 | 3/147 (2%) | 3 | 7/451 (1.6%) | 7 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 5/143 (3.5%) | 5 | 1/62 (1.6%) | 1 |
| Vomiting | 14/1563 (0.9%) | 14 | 0/368 (0%) | 0 | 40/372 (10.8%) | 51 | 14/147 (9.5%) | 18 | 38/451 (8.4%) | 47 | 19/219 (8.7%) | 23 | 3/285 (1.1%) | 3 | 0/80 (0%) | 0 | 14/143 (9.8%) | 16 | 9/62 (14.5%) | 14 |
| General disorders | ||||||||||||||||||||
| Chills | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Facial pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Fatigue | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 9/372 (2.4%) | 10 | 0/147 (0%) | 0 | 4/451 (0.9%) | 4 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 4/143 (2.8%) | 4 | 3/62 (4.8%) | 3 |
| Fever | 12/1563 (0.8%) | 12 | 0/368 (0%) | 0 | 49/372 (13.2%) | 62 | 16/147 (10.9%) | 18 | 42/451 (9.3%) | 48 | 15/219 (6.8%) | 17 | 1/285 (0.4%) | 1 | 1/80 (1.3%) | 1 | 10/143 (7%) | 11 | 7/62 (11.3%) | 9 |
| Flu like symptoms | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Gait disturbance | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| General disorders and administration site conditions - Other, specify | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 2 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypothermia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Infusion related reaction | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Injection site reaction | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Irritability | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Multi-organ failure | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Non-cardiac chest pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Pain | 9/1563 (0.6%) | 9 | 0/368 (0%) | 0 | 5/372 (1.3%) | 7 | 0/147 (0%) | 0 | 10/451 (2.2%) | 10 | 3/219 (1.4%) | 3 | 4/285 (1.4%) | 4 | 0/80 (0%) | 0 | 6/143 (4.2%) | 6 | 1/62 (1.6%) | 1 |
| Hepatobiliary disorders | ||||||||||||||||||||
| Cholecystitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 9/372 (2.4%) | 9 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 3 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 1/80 (1.3%) | 1 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Gallbladder obstruction | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Gallbladder pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hepatic failure | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Hepatic pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hepatobiliary disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 5/451 (1.1%) | 6 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 0/62 (0%) | 0 |
| Portal hypertension | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||
| Allergic reaction | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 17/372 (4.6%) | 18 | 6/147 (4.1%) | 6 | 18/451 (4%) | 18 | 8/219 (3.7%) | 9 | 0/285 (0%) | 0 | 1/80 (1.3%) | 1 | 10/143 (7%) | 10 | 5/62 (8.1%) | 5 |
| Anaphylaxis | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 40/372 (10.8%) | 42 | 10/147 (6.8%) | 10 | 51/451 (11.3%) | 53 | 13/219 (5.9%) | 13 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 10/143 (7%) | 10 | 2/62 (3.2%) | 2 |
| Immune system disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 6/372 (1.6%) | 9 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 6 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Infections and infestations | ||||||||||||||||||||
| Abdominal infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Anorectal infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Appendicitis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 3/147 (2%) | 3 | 6/451 (1.3%) | 6 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Appendicitis perforated | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Biliary tract infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Bladder infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Bone infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Bronchial infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Catheter related infection | 12/1563 (0.8%) | 13 | 0/368 (0%) | 0 | 13/372 (3.5%) | 17 | 3/147 (2%) | 3 | 20/451 (4.4%) | 27 | 9/219 (4.1%) | 13 | 4/285 (1.4%) | 4 | 0/80 (0%) | 0 | 10/143 (7%) | 12 | 3/62 (4.8%) | 3 |
| Conjunctivitis infective | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Cranial nerve infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Device related infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Duodenal infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Endocarditis infective | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Endophthalmitis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Enterocolitis infectious | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 18/372 (4.8%) | 19 | 2/147 (1.4%) | 2 | 15/451 (3.3%) | 17 | 7/219 (3.2%) | 8 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 1/62 (1.6%) | 1 |
| Esophageal infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Eye infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Gum infection | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Hepatic infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hepatitis viral | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Infections and infestations - Other, specify | 102/1563 (6.5%) | 127 | 0/368 (0%) | 0 | 145/372 (39%) | 280 | 41/147 (27.9%) | 61 | 184/451 (40.8%) | 298 | 53/219 (24.2%) | 77 | 15/285 (5.3%) | 17 | 0/80 (0%) | 0 | 31/143 (21.7%) | 35 | 8/62 (12.9%) | 10 |
| Infective myositis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Joint infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Kidney infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Lip infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 2/147 (1.4%) | 2 | 2/451 (0.4%) | 2 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Lung infection | 13/1563 (0.8%) | 14 | 0/368 (0%) | 0 | 38/372 (10.2%) | 44 | 12/147 (8.2%) | 15 | 41/451 (9.1%) | 52 | 14/219 (6.4%) | 16 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 9/143 (6.3%) | 9 | 4/62 (6.5%) | 4 |
| Lymph gland infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Mucosal infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 8/372 (2.2%) | 8 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Nail infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Otitis externa | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Otitis media | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 9/372 (2.4%) | 11 | 4/147 (2.7%) | 4 | 19/451 (4.2%) | 21 | 6/219 (2.7%) | 6 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 8/143 (5.6%) | 9 | 2/62 (3.2%) | 2 |
| Pancreas infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Paronychia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pelvic infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Penile infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Periorbital infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Peripheral nerve infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Peritoneal infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pharyngitis | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 5/372 (1.3%) | 5 | 2/147 (1.4%) | 2 | 2/451 (0.4%) | 2 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Pleural infection | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Rash pustular | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Rhinitis infective | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Salivary gland infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Sepsis | 13/1563 (0.8%) | 13 | 0/368 (0%) | 0 | 7/372 (1.9%) | 7 | 4/147 (2.7%) | 5 | 7/451 (1.6%) | 8 | 2/219 (0.9%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 6/143 (4.2%) | 7 | 1/62 (1.6%) | 1 |
| Sinusitis | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 15/372 (4%) | 20 | 7/147 (4.8%) | 7 | 16/451 (3.5%) | 17 | 4/219 (1.8%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 2/62 (3.2%) | 2 |
| Skin infection | 18/1563 (1.2%) | 19 | 0/368 (0%) | 0 | 28/372 (7.5%) | 33 | 8/147 (5.4%) | 11 | 29/451 (6.4%) | 29 | 13/219 (5.9%) | 15 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 7/143 (4.9%) | 8 | 3/62 (4.8%) | 3 |
| Small intestine infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Soft tissue infection | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 1/372 (0.3%) | 2 | 1/147 (0.7%) | 1 | 6/451 (1.3%) | 7 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 1/62 (1.6%) | 1 |
| Splenic infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Tooth infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Tracheitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 2 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Upper respiratory infection | 7/1563 (0.4%) | 8 | 0/368 (0%) | 0 | 49/372 (13.2%) | 63 | 17/147 (11.6%) | 18 | 45/451 (10%) | 55 | 20/219 (9.1%) | 23 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 17/143 (11.9%) | 23 | 8/62 (12.9%) | 11 |
| Urethral infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urinary tract infection | 7/1563 (0.4%) | 7 | 0/368 (0%) | 0 | 15/372 (4%) | 15 | 2/147 (1.4%) | 2 | 10/451 (2.2%) | 11 | 9/219 (4.1%) | 11 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 8/143 (5.6%) | 9 | 0/62 (0%) | 0 |
| Vaginal infection | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Vulval infection | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Wound infection | 5/1563 (0.3%) | 6 | 0/368 (0%) | 0 | 3/372 (0.8%) | 4 | 0/147 (0%) | 0 | 6/451 (1.3%) | 7 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Bruising | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Fall | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Fracture | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Injury to superior vena cava | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Injury, poisoning and procedural complications - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Postoperative thoracic procedure complication | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Prolapse of intestinal stoma | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Seroma | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vascular access complication | 12/1563 (0.8%) | 12 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 2/219 (0.9%) | 2 | 4/285 (1.4%) | 4 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Venous injury | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Wound complication | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Wound dehiscence | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Investigations | ||||||||||||||||||||
| Activated partial thromboplastin time prolonged | 16/1563 (1%) | 16 | 0/368 (0%) | 0 | 6/372 (1.6%) | 8 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 4/143 (2.8%) | 4 | 0/62 (0%) | 0 |
| Alanine aminotransferase increased | 133/1563 (8.5%) | 133 | 0/368 (0%) | 0 | 157/372 (42.2%) | 456 | 62/147 (42.2%) | 166 | 182/451 (40.4%) | 493 | 83/219 (37.9%) | 217 | 25/285 (8.8%) | 25 | 1/80 (1.3%) | 1 | 49/143 (34.3%) | 97 | 21/62 (33.9%) | 50 |
| Alkaline phosphatase increased | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 7/372 (1.9%) | 7 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 2 |
| Aspartate aminotransferase increased | 72/1563 (4.6%) | 72 | 0/368 (0%) | 0 | 86/372 (23.1%) | 133 | 35/147 (23.8%) | 59 | 99/451 (22%) | 145 | 36/219 (16.4%) | 54 | 6/285 (2.1%) | 6 | 1/80 (1.3%) | 2 | 27/143 (18.9%) | 40 | 10/62 (16.1%) | 12 |
| Blood antidiuretic hormone abnormal | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Blood bilirubin increased | 29/1563 (1.9%) | 29 | 0/368 (0%) | 0 | 42/372 (11.3%) | 66 | 20/147 (13.6%) | 31 | 52/451 (11.5%) | 85 | 20/219 (9.1%) | 40 | 4/285 (1.4%) | 4 | 1/80 (1.3%) | 1 | 25/143 (17.5%) | 29 | 6/62 (9.7%) | 8 |
| Blood gonadotrophin abnormal | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Blood prolactin abnormal | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| CPK increased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Cholesterol high | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 3/372 (0.8%) | 5 | 0/147 (0%) | 0 | 2/451 (0.4%) | 3 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Creatinine increased | 21/1563 (1.3%) | 21 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 0/62 (0%) | 0 |
| Fibrinogen decreased | 75/1563 (4.8%) | 76 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 3/147 (2%) | 4 | 3/451 (0.7%) | 5 | 1/219 (0.5%) | 1 | 8/285 (2.8%) | 8 | 1/80 (1.3%) | 1 | 5/143 (3.5%) | 5 | 0/62 (0%) | 0 |
| GGT increased | 22/1563 (1.4%) | 22 | 0/368 (0%) | 0 | 14/372 (3.8%) | 27 | 3/147 (2%) | 4 | 12/451 (2.7%) | 24 | 6/219 (2.7%) | 9 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 6/143 (4.2%) | 8 | 1/62 (1.6%) | 2 |
| Growth hormone abnormal | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hemoglobin increased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| INR increased | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 0/147 (0%) | 0 | 4/451 (0.9%) | 4 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Investigations - Other, specify | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 4/451 (0.9%) | 4 | 2/219 (0.9%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Lipase increased | 15/1563 (1%) | 15 | 0/368 (0%) | 0 | 15/372 (4%) | 19 | 9/147 (6.1%) | 13 | 26/451 (5.8%) | 31 | 4/219 (1.8%) | 4 | 3/285 (1.1%) | 3 | 1/80 (1.3%) | 1 | 10/143 (7%) | 12 | 3/62 (4.8%) | 3 |
| Lymphocyte count decreased | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 24/372 (6.5%) | 41 | 9/147 (6.1%) | 15 | 28/451 (6.2%) | 44 | 13/219 (5.9%) | 18 | 3/285 (1.1%) | 3 | 0/80 (0%) | 0 | 7/143 (4.9%) | 13 | 3/62 (4.8%) | 5 |
| Neutrophil count decreased | 97/1563 (6.2%) | 98 | 0/368 (0%) | 0 | 276/372 (74.2%) | 710 | 89/147 (60.5%) | 189 | 331/451 (73.4%) | 1010 | 116/219 (53%) | 277 | 8/285 (2.8%) | 8 | 1/80 (1.3%) | 1 | 100/143 (69.9%) | 208 | 35/62 (56.5%) | 76 |
| Platelet count decreased | 61/1563 (3.9%) | 61 | 0/368 (0%) | 0 | 117/372 (31.5%) | 201 | 29/147 (19.7%) | 44 | 150/451 (33.3%) | 251 | 50/219 (22.8%) | 75 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 37/143 (25.9%) | 53 | 13/62 (21%) | 19 |
| Serum amylase increased | 11/1563 (0.7%) | 11 | 0/368 (0%) | 0 | 11/372 (3%) | 13 | 2/147 (1.4%) | 4 | 17/451 (3.8%) | 17 | 5/219 (2.3%) | 5 | 1/285 (0.4%) | 1 | 1/80 (1.3%) | 1 | 5/143 (3.5%) | 5 | 1/62 (1.6%) | 2 |
| Urine output decreased | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Weight gain | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 1/372 (0.3%) | 6 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Weight loss | 17/1563 (1.1%) | 17 | 0/368 (0%) | 0 | 23/372 (6.2%) | 25 | 6/147 (4.1%) | 6 | 16/451 (3.5%) | 17 | 5/219 (2.3%) | 5 | 5/285 (1.8%) | 5 | 0/80 (0%) | 0 | 6/143 (4.2%) | 8 | 3/62 (4.8%) | 3 |
| White blood cell decreased | 54/1563 (3.5%) | 54 | 0/368 (0%) | 0 | 110/372 (29.6%) | 253 | 35/147 (23.8%) | 62 | 125/451 (27.7%) | 353 | 40/219 (18.3%) | 70 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 38/143 (26.6%) | 61 | 11/62 (17.7%) | 18 |
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Acidosis | 7/1563 (0.4%) | 7 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Alkalosis | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Anorexia | 27/1563 (1.7%) | 27 | 0/368 (0%) | 0 | 38/372 (10.2%) | 45 | 17/147 (11.6%) | 35 | 32/451 (7.1%) | 45 | 16/219 (7.3%) | 21 | 4/285 (1.4%) | 4 | 0/80 (0%) | 0 | 12/143 (8.4%) | 13 | 6/62 (9.7%) | 7 |
| Dehydration | 15/1563 (1%) | 15 | 0/368 (0%) | 0 | 51/372 (13.7%) | 62 | 22/147 (15%) | 25 | 30/451 (6.7%) | 34 | 15/219 (6.8%) | 18 | 9/285 (3.2%) | 9 | 0/80 (0%) | 0 | 11/143 (7.7%) | 13 | 7/62 (11.3%) | 7 |
| Glucose intolerance | 8/1563 (0.5%) | 8 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypercalcemia | 10/1563 (0.6%) | 10 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Hyperglycemia | 216/1563 (13.8%) | 217 | 0/368 (0%) | 0 | 14/372 (3.8%) | 16 | 4/147 (2.7%) | 7 | 42/451 (9.3%) | 67 | 14/219 (6.4%) | 22 | 17/285 (6%) | 18 | 0/80 (0%) | 0 | 15/143 (10.5%) | 21 | 2/62 (3.2%) | 2 |
| Hyperkalemia | 80/1563 (5.1%) | 80 | 0/368 (0%) | 0 | 6/372 (1.6%) | 8 | 3/147 (2%) | 4 | 12/451 (2.7%) | 12 | 3/219 (1.4%) | 3 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 4/143 (2.8%) | 4 | 1/62 (1.6%) | 1 |
| Hypermagnesemia | 8/1563 (0.5%) | 8 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Hypernatremia | 9/1563 (0.6%) | 9 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Hypertriglyceridemia | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 10/372 (2.7%) | 12 | 1/147 (0.7%) | 1 | 6/451 (1.3%) | 8 | 1/219 (0.5%) | 1 | 3/285 (1.1%) | 3 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 1/62 (1.6%) | 1 |
| Hyperuricemia | 37/1563 (2.4%) | 37 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypoalbuminemia | 19/1563 (1.2%) | 19 | 0/368 (0%) | 0 | 16/372 (4.3%) | 18 | 4/147 (2.7%) | 6 | 24/451 (5.3%) | 26 | 10/219 (4.6%) | 10 | 10/285 (3.5%) | 10 | 0/80 (0%) | 0 | 7/143 (4.9%) | 9 | 2/62 (3.2%) | 2 |
| Hypocalcemia | 199/1563 (12.7%) | 200 | 0/368 (0%) | 0 | 16/372 (4.3%) | 16 | 6/147 (4.1%) | 6 | 14/451 (3.1%) | 15 | 8/219 (3.7%) | 8 | 6/285 (2.1%) | 6 | 0/80 (0%) | 0 | 5/143 (3.5%) | 5 | 2/62 (3.2%) | 3 |
| Hypoglycemia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 13/372 (3.5%) | 18 | 4/147 (2.7%) | 4 | 9/451 (2%) | 11 | 6/219 (2.7%) | 6 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Hypokalemia | 99/1563 (6.3%) | 100 | 0/368 (0%) | 0 | 58/372 (15.6%) | 71 | 15/147 (10.2%) | 20 | 101/451 (22.4%) | 127 | 41/219 (18.7%) | 48 | 10/285 (3.5%) | 10 | 0/80 (0%) | 0 | 14/143 (9.8%) | 16 | 4/62 (6.5%) | 5 |
| Hypomagnesemia | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hyponatremia | 116/1563 (7.4%) | 116 | 0/368 (0%) | 0 | 16/372 (4.3%) | 17 | 7/147 (4.8%) | 9 | 26/451 (5.8%) | 28 | 10/219 (4.6%) | 10 | 21/285 (7.4%) | 21 | 0/80 (0%) | 0 | 11/143 (7.7%) | 13 | 1/62 (1.6%) | 1 |
| Hypophosphatemia | 44/1563 (2.8%) | 44 | 0/368 (0%) | 0 | 9/372 (2.4%) | 9 | 3/147 (2%) | 3 | 13/451 (2.9%) | 14 | 5/219 (2.3%) | 5 | 6/285 (2.1%) | 6 | 0/80 (0%) | 0 | 6/143 (4.2%) | 7 | 2/62 (3.2%) | 2 |
| Iron overload | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 2/451 (0.4%) | 4 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Metabolism and nutrition disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Obesity | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Tumor lysis syndrome | 135/1563 (8.6%) | 135 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 5/285 (1.8%) | 5 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Arthralgia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 3/372 (0.8%) | 8 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Avascular necrosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 37/372 (9.9%) | 66 | 5/147 (3.4%) | 7 | 34/451 (7.5%) | 51 | 9/219 (4.1%) | 11 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 15/143 (10.5%) | 26 | 7/62 (11.3%) | 11 |
| Back pain | 10/1563 (0.6%) | 10 | 0/368 (0%) | 0 | 9/372 (2.4%) | 10 | 0/147 (0%) | 0 | 10/451 (2.2%) | 11 | 8/219 (3.7%) | 10 | 4/285 (1.4%) | 4 | 0/80 (0%) | 0 | 5/143 (3.5%) | 11 | 2/62 (3.2%) | 2 |
| Bone pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 5/451 (1.1%) | 7 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Buttock pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Chest wall pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Flank pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Generalized muscle weakness | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Joint effusion | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Joint range of motion decreased | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Muscle weakness left-sided | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Muscle weakness lower limb | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Muscle weakness right-sided | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Muscle weakness trunk | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Muscle weakness upper limb | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Musculoskeletal and connective tissue disorder - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Myalgia | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Myositis | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Neck pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Osteoporosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pain in extremity | 11/1563 (0.7%) | 11 | 0/368 (0%) | 0 | 17/372 (4.6%) | 17 | 6/147 (4.1%) | 6 | 10/451 (2.2%) | 12 | 5/219 (2.3%) | 7 | 6/285 (2.1%) | 6 | 0/80 (0%) | 0 | 4/143 (2.8%) | 4 | 1/62 (1.6%) | 3 |
| Scoliosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 3 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Myelodysplastic syndrome | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Tumor pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||
| Abducens nerve disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Amnesia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Ataxia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 1/147 (0.7%) | 2 | 3/451 (0.7%) | 3 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Cerebrospinal fluid leakage | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 1/62 (1.6%) | 1 |
| Cognitive disturbance | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 5/372 (1.3%) | 5 | 1/147 (0.7%) | 1 | 7/451 (1.6%) | 8 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Concentration impairment | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Depressed level of consciousness | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 9/372 (2.4%) | 10 | 2/147 (1.4%) | 2 | 7/451 (1.6%) | 7 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Dizziness | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 9/372 (2.4%) | 11 | 5/147 (3.4%) | 12 | 4/451 (0.9%) | 6 | 10/219 (4.6%) | 14 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 2/143 (1.4%) | 3 | 1/62 (1.6%) | 1 |
| Dysarthria | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 3/219 (1.4%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 0/62 (0%) | 0 |
| Dysesthesia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Dysgeusia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dysphasia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Encephalopathy | 9/1563 (0.6%) | 9 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 8/451 (1.8%) | 8 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 0/62 (0%) | 0 |
| Extrapyramidal disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 4/451 (0.9%) | 4 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Facial muscle weakness | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Facial nerve disorder | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 3 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Headache | 43/1563 (2.8%) | 44 | 0/368 (0%) | 0 | 37/372 (9.9%) | 65 | 16/147 (10.9%) | 33 | 37/451 (8.2%) | 68 | 34/219 (15.5%) | 55 | 12/285 (4.2%) | 12 | 1/80 (1.3%) | 1 | 19/143 (13.3%) | 32 | 9/62 (14.5%) | 25 |
| Hydrocephalus | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypersomnia | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| IVth nerve disorder | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Intracranial hemorrhage | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Ischemia cerebrovascular | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Lethargy | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 2/372 (0.5%) | 3 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Leukoencephalopathy | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 6/372 (1.6%) | 6 | 4/147 (2.7%) | 4 | 10/451 (2.2%) | 10 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 2/62 (3.2%) | 2 |
| Memory impairment | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 2/147 (1.4%) | 2 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 2 |
| Meningismus | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Movements involuntary | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Nervous system disorders - Other, specify | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 6/372 (1.6%) | 6 | 1/147 (0.7%) | 1 | 12/451 (2.7%) | 13 | 3/219 (1.4%) | 3 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 0/62 (0%) | 0 |
| Neuralgia | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 6/372 (1.6%) | 7 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Oculomotor nerve disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 3/372 (0.8%) | 4 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Paresthesia | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 2/147 (1.4%) | 2 | 1/451 (0.2%) | 1 | 3/219 (1.4%) | 3 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 4/143 (2.8%) | 5 | 4/62 (6.5%) | 6 |
| Peripheral motor neuropathy | 87/1563 (5.6%) | 87 | 0/368 (0%) | 0 | 116/372 (31.2%) | 335 | 45/147 (30.6%) | 129 | 106/451 (23.5%) | 273 | 57/219 (26%) | 148 | 8/285 (2.8%) | 8 | 1/80 (1.3%) | 1 | 31/143 (21.7%) | 72 | 23/62 (37.1%) | 41 |
| Peripheral sensory neuropathy | 181/1563 (11.6%) | 183 | 0/368 (0%) | 0 | 106/372 (28.5%) | 273 | 41/147 (27.9%) | 118 | 91/451 (20.2%) | 262 | 46/219 (21%) | 132 | 38/285 (13.3%) | 38 | 0/80 (0%) | 0 | 33/143 (23.1%) | 98 | 20/62 (32.3%) | 60 |
| Presyncope | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 2/147 (1.4%) | 2 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pyramidal tract syndrome | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Reversible posterior leukoencephalopathy syndrome | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Seizure | 31/1563 (2%) | 32 | 0/368 (0%) | 0 | 12/372 (3.2%) | 20 | 2/147 (1.4%) | 2 | 19/451 (4.2%) | 20 | 4/219 (1.8%) | 4 | 2/285 (0.7%) | 2 | 1/80 (1.3%) | 1 | 3/143 (2.1%) | 3 | 3/62 (4.8%) | 4 |
| Somnolence | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 8/147 (5.4%) | 8 | 10/451 (2.2%) | 10 | 11/219 (5%) | 12 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Stroke | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Syncope | 7/1563 (0.4%) | 8 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 3/147 (2%) | 3 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 4/143 (2.8%) | 4 | 4/62 (6.5%) | 4 |
| Transient ischemic attacks | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 3 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Tremor | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 5/372 (1.3%) | 7 | 5/147 (3.4%) | 6 | 3/451 (0.7%) | 3 | 6/219 (2.7%) | 6 | 2/285 (0.7%) | 3 | 0/80 (0%) | 0 | 1/143 (0.7%) | 2 | 2/62 (3.2%) | 2 |
| Trigeminal nerve disorder | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vagus nerve disorder | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vasovagal reaction | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||
| Agitation | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 2/147 (1.4%) | 2 | 3/451 (0.7%) | 3 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 2/62 (3.2%) | 3 |
| Anxiety | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 8/372 (2.2%) | 8 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Confusion | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Delirium | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Depression | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 7/372 (1.9%) | 8 | 2/147 (1.4%) | 2 | 4/451 (0.9%) | 4 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Euphoria | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hallucinations | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Insomnia | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Personality change | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Psychiatric disorders - Other, specify | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Psychosis | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 0/147 (0%) | 0 | 5/451 (1.1%) | 5 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Suicidal ideation | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 4 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Suicide attempt | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||
| Acute kidney injury | 24/1563 (1.5%) | 24 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 3 | 2/219 (0.9%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 3 | 0/62 (0%) | 0 |
| Chronic kidney disease | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Cystitis noninfective | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hematuria | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Proteinuria | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Renal and urinary disorders - Other, specify | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Renal calculi | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 4/372 (1.1%) | 5 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 3 |
| Renal colic | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Renal hemorrhage | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urinary frequency | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urinary retention | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urinary tract obstruction | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urinary tract pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||
| Pelvic pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Perineal pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Testicular pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vaginal dryness | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vaginal inflammation | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Vaginal pain | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Adult respiratory distress syndrome | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Allergic rhinitis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Aspiration | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Atelectasis | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 2/143 (1.4%) | 3 | 0/62 (0%) | 0 |
| Bronchial obstruction | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Bronchopulmonary hemorrhage | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Bronchospasm | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Cough | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 5/372 (1.3%) | 5 | 0/147 (0%) | 0 | 4/451 (0.9%) | 4 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Dyspnea | 6/1563 (0.4%) | 6 | 0/368 (0%) | 0 | 3/372 (0.8%) | 3 | 3/147 (2%) | 3 | 2/451 (0.4%) | 2 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 1/62 (1.6%) | 2 |
| Epistaxis | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 5/372 (1.3%) | 5 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 3/219 (1.4%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Hoarseness | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypoxia | 31/1563 (2%) | 31 | 0/368 (0%) | 0 | 11/372 (3%) | 12 | 3/147 (2%) | 3 | 12/451 (2.7%) | 12 | 3/219 (1.4%) | 4 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 3/143 (2.1%) | 3 | 1/62 (1.6%) | 1 |
| Laryngeal edema | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Nasal congestion | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pharyngeal mucositis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Pharyngolaryngeal pain | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 3/451 (0.7%) | 3 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pleural effusion | 16/1563 (1%) | 16 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 0/147 (0%) | 0 | 4/451 (0.9%) | 4 | 1/219 (0.5%) | 2 | 10/285 (3.5%) | 10 | 0/80 (0%) | 0 | 5/143 (3.5%) | 5 | 0/62 (0%) | 0 |
| Pleural hemorrhage | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pneumonitis | 7/1563 (0.4%) | 7 | 0/368 (0%) | 0 | 6/372 (1.6%) | 6 | 2/147 (1.4%) | 3 | 7/451 (1.6%) | 7 | 2/219 (0.9%) | 2 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 0/62 (0%) | 0 |
| Pneumothorax | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pulmonary edema | 5/1563 (0.3%) | 5 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Pulmonary fibrosis | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Respiratory failure | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 3/219 (1.4%) | 3 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 2/143 (1.4%) | 2 | 1/62 (1.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 1/451 (0.2%) | 1 | 2/219 (0.9%) | 2 | 1/285 (0.4%) | 1 | 1/80 (1.3%) | 2 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Sore throat | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Stridor | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Wheezing | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Erythema multiforme | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pain of skin | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Palmar-plantar erythrodysesthesia syndrome | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 2/451 (0.4%) | 2 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Photosensitivity | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Pruritus | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 0/147 (0%) | 0 | 7/451 (1.6%) | 8 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Purpura | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Rash maculo-papular | 4/1563 (0.3%) | 4 | 0/368 (0%) | 0 | 2/372 (0.5%) | 4 | 1/147 (0.7%) | 1 | 9/451 (2%) | 9 | 1/219 (0.5%) | 2 | 1/285 (0.4%) | 1 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 2/372 (0.5%) | 2 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 4 | 3/219 (1.4%) | 5 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Skin ulceration | 2/1563 (0.1%) | 2 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 2/451 (0.4%) | 2 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Stevens-Johnson syndrome | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Urticaria | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 4/372 (1.1%) | 4 | 2/147 (1.4%) | 2 | 3/451 (0.7%) | 3 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Social circumstances | ||||||||||||||||||||
| Social circumstances - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 1/62 (1.6%) | 1 |
| Surgical and medical procedures | ||||||||||||||||||||
| Surgical and medical procedures - Other, specify | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 1/372 (0.3%) | 1 | 1/147 (0.7%) | 1 | 0/451 (0%) | 0 | 1/219 (0.5%) | 1 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||
| Capillary leak syndrome | 0/1563 (0%) | 0 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Hematoma | 3/1563 (0.2%) | 3 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 0/451 (0%) | 0 | 0/219 (0%) | 0 | 0/285 (0%) | 0 | 0/80 (0%) | 0 | 1/143 (0.7%) | 1 | 0/62 (0%) | 0 |
| Hypertension | 62/1563 (4%) | 62 | 0/368 (0%) | 0 | 4/372 (1.1%) | 14 | 1/147 (0.7%) | 1 | 10/451 (2.2%) | 11 | 3/219 (1.4%) | 4 | 8/285 (2.8%) | 8 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
| Hypotension | 20/1563 (1.3%) | 20 | 0/368 (0%) | 0 | 14/372 (3.8%) | 14 | 4/147 (2.7%) | 4 | 10/451 (2.2%) | 11 | 6/219 (2.7%) | 6 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 10/143 (7%) | 10 | 6/62 (9.7%) | 7 |
| Thromboembolic event | 25/1563 (1.6%) | 25 | 0/368 (0%) | 0 | 7/372 (1.9%) | 7 | 1/147 (0.7%) | 1 | 3/451 (0.7%) | 3 | 3/219 (1.4%) | 3 | 16/285 (5.6%) | 16 | 0/80 (0%) | 0 | 6/143 (4.2%) | 6 | 2/62 (3.2%) | 2 |
| Vascular disorders - Other, specify | 1/1563 (0.1%) | 1 | 0/368 (0%) | 0 | 0/372 (0%) | 0 | 0/147 (0%) | 0 | 1/451 (0.2%) | 1 | 0/219 (0%) | 0 | 2/285 (0.7%) | 2 | 0/80 (0%) | 0 | 0/143 (0%) | 0 | 0/62 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Results Reporting Coordinator |
|---|---|
| Organization | Children's Oncology Group |
| Phone | 626-447-0064 |
| resultsreportingcoordinator@childrensoncologygroup.org |
Responsible Party:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00408005
Other Study ID Numbers:
- NCI-2009-00307
- NCI-2009-00307
- COG-AALL0434
- 07-169
- CDR0000514500
- AALL0434
- AALL0434
- U10CA098543
- U10CA180886
First Posted:
Dec 5, 2006
Last Update Posted:
Jul 28, 2022
Last Verified:
Mar 1, 2022