Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia
Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00061945
Collaborator
(none)
302
1
1
112
2.7
Study Details
Study Description
Brief Summary
This phase I/II trial studies the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with untreated acute lymphoblastic leukemia. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy also work in different ways to kill cancer cells or stop them from growing. Giving alemtuzumab together with combination chemotherapy may be a better way to block cancer growth.
Detailed Description
PRIMARY OBJECTIVES:
-
To determine the feasibility and toxicity profiles of escalating doses of Campath-1H (alemtuzumab) given subcutaneously during post-remission intensification treatment of adults with acute lymphoblastic leukemia (ALL).
-
To determine the disease-free survival (DFS) and overall survival (OS) when Campath-1H is used during post-remission intensification treatment of adults with ALL.
-
To determine whether antibody treatment with Campath-1H can further reduce minimal residual disease states in adult ALL.
-
To obtain preliminary descriptive data on serum levels of Campath-1H during course IV, module D using limited pharmacokinetic sampling during the phase I and II components of the study.
-
To obtain feasibility data on the addition of imatinib to Cancer and Leukemia Group B (CALGB) induction and postremission combination chemotherapy for patients with Philadelphia chromosome positive (Ph+) ALL.
OUTLINE: This is a dose-escalation study of alemtuzumab.
COURSE 1 (module A): Patients receive allopurinol orally (PO) 4 times daily (QID) on days 1-14, cyclophosphamide* intravenously (IV) over 15-30 minutes on day 1, daunorubicin hydrochloride IV on days 1-3, vincristine sulfate IV on days 1, 8, 15, and 22, dexamethasone PO twice daily (BID) on days 1-7 and 15-21, asparaginase subcutaneously (SC) on days 5, 8, 11, 15, 18, and 22, and filgrastim SC on days 4-11. Patients who are Ph+ also receive imatinib mesylate PO on days 15-28.
*Note: Patients who are = 60 years old do not receive cyclophosphamide.
COURSE 2 (module B): Patients receive methotrexate intrathecally (IT) on day 1, cytarabine IV over 3 hours on days 1-3, dexamethasone as eye drops QID on days 1-4, trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-29, and cyclophosphamide, asparaginase and filgrastim as in course 1. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28.
COURSE 3 (module C): Patients receive vincristine sulfate IV on days 1, 15, and 29, methotrexate IV over 3 hours and IT on days 1, 15, and 19, methotrexate PO every 6 hours on days 1-2, 15-16, and 29-30, mercaptopurine PO on days 1-35, leucovorin calcium IV on days 2, 16, and 30, leucovorin calcium PO every 6 hours on days 3-4, and trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-43. Patients who are Ph+ also receive imatinib mesylate PO on days 1-42.
COURSE 4 (module D): Patients receive alemtuzumab SC 3 times weekly for 4 weeks and begin acyclovir PO QID for 6 months (continuing through course 8).
-
Phase I Cohort 1: 10 mg
-
Phase I Cohort 2: 20 mg
-
Phase I Cohort 3/Phase II MTD: 30 mg
COURSE 5 (module A): Patients repeat course 1, minus allopurinol.
COURSE 6 (module B): Patients repeat course 2.
COURSE 7 (module C): Patients repeat course 3.
COURSE 8: Patients receive mercaptopurine PO, vincristine sulfate IV on day 1, dexamethasone PO on days 1-5, methotrexate PO on days 1, 8, 15, and 22, and trimethoprim-sulfamethoxazole PO BID 3 days weekly. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 10 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
302 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Dose Escalation Study of Subcutaneous Campath-1H (NSC #715969, IND #10864) During Intensification Therapy in Adults With Untreated Acute Lymphoblastic Leukemia (ALL)
Study Start Date
:
Jun 1, 2003
Actual Primary Completion Date
:
Dec 1, 2007
Actual Study Completion Date
:
Oct 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (alemtuzumab and combination chemotherapy) See detailed description. |
Drug: allopurinol
Given PO
Drug: cyclophosphamide
Given IV
Drug: daunorubicin hydrochloride
Given IV
Drug: vincristine sulfate
Given IV
Drug: dexamethasone
Given PO and as eye drops
Drug: asparaginase
Given SC
Biological: filgrastim
Given SC
Drug: imatinib mesylate
Given PO
Drug: methotrexate
Given IT, IV, and PO
Drug: cytarabine
Given IV
Drug: trimethoprim-sulfamethoxazole
Given PO
Drug: mercaptopurine
Given PO
Drug: leucovorin calcium
Given IV and PO
Biological: alemtuzumab
Given SC
Drug: acyclovir
Given PO
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I) [6 weeks]
The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data.
- Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II) [8 months]
The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV.
Secondary Outcome Measures
- Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II) [9 years 4 months]
Minimal Residual Disease measures the presence of of circulating leukemia cells in the body. Patients that report a Complete Response (CR) during treatment are further tested to determine the presence of small amounts of circulating leukemia cells. Here we report the number of patients who were MRD negative.
- Disease-free Survival, for Only Complete Response Patients [9 years 4 months]
Disease Free Survival (DFS) is defined as the time from a Complete Response (CR) until death or relapse. The date of last clinical assesment will be used as the censor date for patients with no death or relapse. The DFS will be estimated using the Kaplan-Meier method with confidence intervals presented.
- Overall Survival [9 years 4 months]
Overall Survival is defines as the time from registration to death due to any cause. It is estimated using the Kaplan-Meier method with confidence intervals presented.
Eligibility Criteria
Criteria
Ages Eligible for Study:
15 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Unequivocal histologic diagnosis of precursor B or precursor T lymphoblastic leukemia (World Health Organization [WHO] classification), L1 or L2 ALL or acute undifferentiated leukemia (AUL) (French-American-British Cooperative group [FAB] Classification); Burkitt-type ALL (FAB L3, surface immunoglobulin [SIg]+) are excluded
-
No prior treatment for leukemia with three permissible exceptions:
-
Emergency leukapheresis II. Emergency treatment for hyperleukocytosis with hydroxyurea III. Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
-
All patients must have a pre-treatment bone marrow or peripheral blood sample submitted for central immunophenotyping; only those patients who express CD52 >= 10% in the leukemia blast cell channel will be eligible to receive Campath-1H during module D, course IV
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer and Leukemia Group B | Chicago | Illinois | United States | 60606 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Wendy Stock, Cancer and Leukemia Group B
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00061945
Other Study ID Numbers:
- NCI-2012-02807
- NCI-2012-02807
- CDR302482
- CALGB 10102
- CALGB-10102
- U10CA031946
First Posted:
Jun 6, 2003
Last Update Posted:
May 3, 2022
Last Verified:
Apr 1, 2022
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | From June 2003 to May 2007, a total of 302 participants were recruited. |
|---|---|
| Pre-assignment Detail | Two (2) participants cancelled prior to receiving any treatment and were removed from all analyses. |
| Arm/Group Title | Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy |
|---|---|---|
| Arm/Group Description | COURSE 1-allopurinol (ALL) orally (PO) 4x daily (QID) d1-14, cyclophosphamide (CTX) intravenously (IV) d1, daunorubicin IV d1-3, vincristine (VCR) IV d1,8,15 & 22, dexamethasone (DEX) PO 2x daily (BID) d1-7 & 15-21, asparaginase (APG) subcutaneously (SC) d5,8,11,15,18 & 22, and filgrastim (FIL) SC d4-11. Ph+ pts imatinib (IMT) PO d15-28 COURSE 2-methotrexate (MTX) intrathecally (IT) d1, cytarabine IV d1-3, DEX eye drops QID d1-4, cotrimoxazole (CRT) PO BID 3x wkly d1-29 and CTX, APG & FIL as course 1. Ph+ pts IMT PO d1-28 COURSE 3-VCR IV d1,15 & 29, MTX IV & IT d1,15 & 19, MTX PO q6 hr d1-2,15-16 & 29-30, mercaptopurine (6-MP) PO d1-35, leucovorin (LCV) IV d 2,16 & 30, LCV PO q6 hr d3-4 & CRT PO BID 3x wkly d1-43. Ph+ pts IMT PO d1-42 COURSE 4-alemtuzumab 10,20 or 30 mg SC 3x wkly q4 wk, acyclovir PO QID q6 mo COURSE 5-course 1 COURSE 6-course 2 COURSE 7-course 3 COURSE 8-6-MP PO, VCR IV d1, DEX PO d1-5, MTX PO d1,8,15 & 22 and CRT PO BID 3d wkly. Ph+ pts IMT PO d1-28 q24 mo | COURSE 1-allopurinol (ALL) orally (PO) 4x daily (QID) d1-14, cyclophosphamide (CTX) intravenously (IV) d1, daunorubicin IV d1-3, vincristine (VCR) IV d 1,8,15 & 22, dexamethasone (DEX) PO 2x daily (BID) d 1-7 & 15-21, asparaginase (APG) subcutaneously (SC) d 5,8,11,15,18 & 22, and filgrastim (FIL) SC d 4-11. Ph+ pts imatinib (IMT) PO d 15-28 COURSE 2-methotrexate (MTX) intrathecally (IT) d1, cytarabine IV d1-3, DEX eye drops QID d 1-4, cotrimoxazole (CRT) PO BID 3x wkly d1-29 and CTX, APG & FIL as course 1. Ph+ pts IMT PO d1-28 COURSE 3-VCR IV d 1,15 & 29, MTX IV & IT d 1,15 & 19, MTX PO q6 hr d 1-2,15-16 & 29-30, mercaptopurine (6-MP) PO d1-35, leucovorin (LCV) IV d 2,16 & 30, LCV PO q6 hr d 3-4 & CRT PO BID 3x wkly d1-43. Ph+ pts IMT PO d1-42 COURSE 4-alemtuzumab 30 mg SC 3x wkly q4 wk, acyclovir PO QID q6 mo COURSE 5-course 1 COURSE 6-course 2 COURSE 7-course 3 COURSE 8-6-MP PO, VCR IV d1, DEX PO d1-5, MTX PO d 1,8,15 & 22 and CRT PO BID 3x wkly. Ph+ pts IMT PO d1-28 q24 mo |
| Period Title: Registration Through Course 3 | ||
| STARTED | 119 | 181 |
| COMPLETED | 25 | 66 |
| NOT COMPLETED | 94 | 115 |
| Period Title: Registration Through Course 3 | ||
| STARTED | 25 | 66 |
| COMPLETED | 18 | 50 |
| NOT COMPLETED | 7 | 16 |
Baseline Characteristics
| Arm/Group Title | Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy | Total |
|---|---|---|---|
| Arm/Group Description | See detailed description or participant flow. | See detailed description or participant flow. | Total of all reporting groups |
| Overall Participants | 119 | 181 | 300 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
48.3
|
46.5
|
46.8
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
55
46.2%
|
73
40.3%
|
128
42.7%
|
| Male |
64
53.8%
|
108
59.7%
|
172
57.3%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
1
0.6%
|
1
0.3%
|
| Asian |
5
4.2%
|
4
2.2%
|
9
3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
11
9.2%
|
17
9.4%
|
28
9.3%
|
| White |
101
84.9%
|
150
82.9%
|
251
83.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
1.7%
|
9
5%
|
11
3.7%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
119
100%
|
181
100%
|
300
100%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I) |
|---|---|
| Description | The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants who started Alemtuzumab were analyzed per study design. Specifically, one patient declined Alemtuzumab and was excluded from this analysis. |
| Arm/Group Title | Phase I - Alemtuzumab and Combination Chemotherapy |
|---|---|
| Arm/Group Description | See detailed description or participant flow. |
| Measure Participants | 24 |
| Number [mg] |
30
|
| Title | Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II) |
|---|---|
| Description | The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV. |
| Time Frame | 8 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants who started Alemtuzumab were analyzed per study design. Specifically, one patient declined Alemtuzumab and was excluded from this analysis. |
| Arm/Group Title | Phase II - Alemtuzumab and Combination Chemotherapy |
|---|---|
| Arm/Group Description | See detailed description or participant flow. |
| Measure Participants | 65 |
| Number [participants] |
30
25.2%
|
| Title | Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II) |
|---|---|
| Description | Minimal Residual Disease measures the presence of of circulating leukemia cells in the body. Patients that report a Complete Response (CR) during treatment are further tested to determine the presence of small amounts of circulating leukemia cells. Here we report the number of patients who were MRD negative. |
| Time Frame | 9 years 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients who reported a Complete Response (CR) during treatment and were analyzed for the presence of circulating leukemia cells. |
| Arm/Group Title | Phase II - Alemtuzumab and Combination Chemotherapy |
|---|---|
| Arm/Group Description | See detailed description or participant flow. |
| Measure Participants | 51 |
| Count of Participants [Participants] |
16
13.4%
|
| Title | Disease-free Survival, for Only Complete Response Patients |
|---|---|
| Description | Disease Free Survival (DFS) is defined as the time from a Complete Response (CR) until death or relapse. The date of last clinical assesment will be used as the censor date for patients with no death or relapse. The DFS will be estimated using the Kaplan-Meier method with confidence intervals presented. |
| Time Frame | 9 years 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received protocol treatment and had a complete response (CR) during treatment were included in this analysis. Phase I patients, who achieved complete response, were included with the phase II patients, who achieved complete response, for this analysis. |
| Arm/Group Title | Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy |
|---|---|---|
| Arm/Group Description | See detailed description or participant flow. | See detailed description or participant flow. |
| Measure Participants | 92 | 145 |
| Median (95% Confidence Interval) [months] |
58.6
|
19.8
|
| Title | Overall Survival |
|---|---|
| Description | Overall Survival is defines as the time from registration to death due to any cause. It is estimated using the Kaplan-Meier method with confidence intervals presented. |
| Time Frame | 9 years 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who registered, received protocol treatment, and were eligible were evaluated for this endpoint. Phase I patients were included with the phase II patients for this analysis. |
| Arm/Group Title | Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy |
|---|---|---|
| Arm/Group Description | See detailed description or participant flow. | See detailed description or participant flow. |
| Measure Participants | 116 | 181 |
| Median (95% Confidence Interval) [months] |
33.6
|
23.1
|
| Title | Number of Participants Achieving Complete Remission |
|---|---|
| Description | A complete remission (CR) requires the following: an absolute neutrophil count (segs and bands) > 1500/μl, no circulating blasts, platelets > 100,000/μl; bone marrow cellularity > 20% with trilineage hematopoiesis, and < 5% marrow blast cells, none of which appear neoplastic. All previous extramedullary manifestations of disease must be absent (e.g., lymphadenopathy, splenomegaly, skin or gum infiltration, testicular masses, or CNS involvement). |
| Time Frame | 9 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Three participants were deemed ineligible and excluded from this analysis. |
| Arm/Group Title | Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy |
|---|---|---|
| Arm/Group Description | See detailed description | See detailed description |
| Measure Participants | 116 | 181 |
| Number [participants] |
92
77.3%
|
145
80.1%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy | ||
| Arm/Group Description | See detailed description or participant flow. | See detailed description or participant flow. | ||
All Cause Mortality |
||||
| Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 60/119 (50.4%) | 98/181 (54.1%) | ||
| Blood and lymphatic system disorders | ||||
| Disseminated intravascular coagulation | 3/119 (2.5%) | 3 | 5/181 (2.8%) | 5 |
| Febrile neutropenia | 32/119 (26.9%) | 35 | 44/181 (24.3%) | 52 |
| Hemoglobin decreased | 59/119 (49.6%) | 86 | 92/181 (50.8%) | 146 |
| Lymphatic disorder | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Cardiac disorders | ||||
| Arrhythmia supraventricular | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Asystole | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Atrial fibrillation | 3/119 (2.5%) | 3 | 5/181 (2.8%) | 6 |
| Atrial tachycardia | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cardiac disorder | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Cardiac pain | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Cardiac valve disease | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cardiopulmonary arrest | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Conduction disorder | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Left ventricular dysfunction | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Left ventricular failure | 5/119 (4.2%) | 6 | 6/181 (3.3%) | 8 |
| Myocardial ischemia | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Palpitations | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Pericardial effusion | 0/119 (0%) | 0 | 4/181 (2.2%) | 5 |
| Sinus bradycardia | 2/119 (1.7%) | 2 | 2/181 (1.1%) | 2 |
| Sinus tachycardia | 5/119 (4.2%) | 6 | 10/181 (5.5%) | 12 |
| Supraventricular tachycardia | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Ventricular bigeminy | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Ear and labyrinth disorders | ||||
| Ear pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Hearing impaired | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Middle ear inflammation | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Hyperthyroidism | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Eye disorders | ||||
| Conjunctivitis | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Diplopia | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Dry eye syndrome | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Eye disorder | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Eye pain | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Optic nerve disorder | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Photophobia | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Proptosis | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Vision blurred | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Vitreous hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 3/119 (2.5%) | 3 | 2/181 (1.1%) | 2 |
| Abdominal pain | 12/119 (10.1%) | 12 | 26/181 (14.4%) | 29 |
| Anal hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Ascites | 4/119 (3.4%) | 4 | 2/181 (1.1%) | 2 |
| Colitis | 1/119 (0.8%) | 1 | 9/181 (5%) | 11 |
| Colonic hemorrhage | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Colonic perforation | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Constipation | 14/119 (11.8%) | 15 | 21/181 (11.6%) | 26 |
| Diarrhea | 20/119 (16.8%) | 23 | 48/181 (26.5%) | 59 |
| Dry mouth | 0/119 (0%) | 0 | 4/181 (2.2%) | 4 |
| Dyspepsia | 6/119 (5%) | 6 | 11/181 (6.1%) | 11 |
| Dysphagia | 2/119 (1.7%) | 2 | 10/181 (5.5%) | 10 |
| Ear, nose and throat examination abnormal | 9/119 (7.6%) | 9 | 18/181 (9.9%) | 19 |
| Endoscopy large bowel abnormal | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Enteritis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Esophageal pain | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Esophagitis | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Flatulence | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Gastritis | 2/119 (1.7%) | 2 | 4/181 (2.2%) | 4 |
| Gastrointestinal disorder | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 5 |
| Gingival pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 2 |
| Hemorrhoids | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Ileal obstruction | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Ileus | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 4 |
| Intestinal necrosis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Lower gastrointestinal hemorrhage | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Mucositis oral | 13/119 (10.9%) | 13 | 14/181 (7.7%) | 15 |
| Nausea | 28/119 (23.5%) | 35 | 55/181 (30.4%) | 78 |
| Oesophagoscopy abnormal | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Oral hemorrhage | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Oral pain | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Pancreatitis | 2/119 (1.7%) | 2 | 6/181 (3.3%) | 7 |
| Periodontal disease | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Proctitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Rectal fistula | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Rectal hemorrhage | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Rectal pain | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Retroperitoneal hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Small intestinal obstruction | 0/119 (0%) | 0 | 1/181 (0.6%) | 2 |
| Stomach pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Toothache | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Typhlitis | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Upper gastrointestinal hemorrhage | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Vomiting | 18/119 (15.1%) | 21 | 40/181 (22.1%) | 53 |
| General disorders | ||||
| Chest pain | 3/119 (2.5%) | 4 | 7/181 (3.9%) | 8 |
| Chills | 9/119 (7.6%) | 9 | 16/181 (8.8%) | 20 |
| Edema limbs | 15/119 (12.6%) | 18 | 26/181 (14.4%) | 35 |
| Facial pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Fatigue | 33/119 (27.7%) | 42 | 54/181 (29.8%) | 82 |
| Fever | 6/119 (5%) | 7 | 25/181 (13.8%) | 33 |
| Gait abnormal | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| General symptom | 3/119 (2.5%) | 3 | 0/181 (0%) | 0 |
| Ill-defined disorder | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Injection site reaction | 4/119 (3.4%) | 4 | 2/181 (1.1%) | 2 |
| Irritability | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Localized edema | 0/119 (0%) | 0 | 4/181 (2.2%) | 5 |
| Multi-organ failure | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Pain | 5/119 (4.2%) | 5 | 6/181 (3.3%) | 6 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Hepatic failure | 3/119 (2.5%) | 3 | 7/181 (3.9%) | 7 |
| Immune system disorders | ||||
| Hypersensitivity | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Infections and infestations | ||||
| Abdominal infection | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Anorectal infection | 0/119 (0%) | 0 | 4/181 (2.2%) | 4 |
| Biliary tract infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Bladder infection | 1/119 (0.8%) | 1 | 6/181 (3.3%) | 6 |
| Bronchitis | 0/119 (0%) | 0 | 2/181 (1.1%) | 3 |
| Catheter related infection | 6/119 (5%) | 6 | 9/181 (5%) | 11 |
| Conjunctivitis infective | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Device related infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Encephalitis infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Encephalomyelitis infection | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Endocarditis infective | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Eye infection | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Gingival infection | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Hepatic infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 2 |
| Infection | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Infectious colitis | 3/119 (2.5%) | 3 | 1/181 (0.6%) | 1 |
| Infectious meningitis | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Joint infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Lip infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Mucosal infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Opportunistic infection | 3/119 (2.5%) | 3 | 4/181 (2.2%) | 4 |
| Peripheral nerve infection | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Pharyngitis | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Pleural infection | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Pneumonia | 9/119 (7.6%) | 11 | 16/181 (8.8%) | 20 |
| Rhinitis infective | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Scrotal infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Sepsis | 24/119 (20.2%) | 27 | 52/181 (28.7%) | 68 |
| Sinusitis | 2/119 (1.7%) | 2 | 6/181 (3.3%) | 6 |
| Skin infection | 4/119 (3.4%) | 4 | 9/181 (5%) | 9 |
| Small intestine infection | 1/119 (0.8%) | 2 | 2/181 (1.1%) | 2 |
| Soft tissue infection | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Spinal cord infection | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Upper aerodigestive tract infection | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Upper respiratory infection | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Ureteritis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Urethral infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Urinary tract infection | 6/119 (5%) | 6 | 8/181 (4.4%) | 9 |
| Vaginal infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Viral hepatitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Vulval infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Wound infection | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Bruising | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Dermatitis radiation | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Esophageal anastomotic leak | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Prolonged intubation after pulmonary resection (>24 hrs after surgery) | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Seroma | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Vascular access complication | 0/119 (0%) | 0 | 4/181 (2.2%) | 4 |
| Wound dehiscence | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 11/119 (9.2%) | 12 | 24/181 (13.3%) | 29 |
| Alanine aminotransferase increased | 31/119 (26.1%) | 39 | 61/181 (33.7%) | 83 |
| Alkaline phosphatase increased | 16/119 (13.4%) | 21 | 44/181 (24.3%) | 48 |
| Amylase increased | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Aspartate aminotransferase increased | 33/119 (27.7%) | 39 | 61/181 (33.7%) | 82 |
| Blood bilirubin increased | 48/119 (40.3%) | 54 | 59/181 (32.6%) | 79 |
| CD4 lymphocytes decreased | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cardiac troponin T increased | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 6 |
| Coagulopathy | 2/119 (1.7%) | 2 | 7/181 (3.9%) | 7 |
| Creatinine increased | 25/119 (21%) | 27 | 37/181 (20.4%) | 50 |
| Electrocardiogram QTc interval prolonged | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Fibrinogen decreased | 25/119 (21%) | 25 | 40/181 (22.1%) | 42 |
| Gamma-glutamyltransferase increased | 5/119 (4.2%) | 7 | 2/181 (1.1%) | 2 |
| INR increased | 3/119 (2.5%) | 3 | 15/181 (8.3%) | 22 |
| Laboratory test abnormal | 3/119 (2.5%) | 3 | 4/181 (2.2%) | 10 |
| Leukocyte count decreased | 9/119 (7.6%) | 11 | 22/181 (12.2%) | 37 |
| Lipase increased | 0/119 (0%) | 0 | 10/181 (5.5%) | 11 |
| Lymphocyte count decreased | 5/119 (4.2%) | 7 | 13/181 (7.2%) | 16 |
| Neutrophil count decreased | 59/119 (49.6%) | 81 | 90/181 (49.7%) | 137 |
| Platelet count decreased | 59/119 (49.6%) | 80 | 89/181 (49.2%) | 141 |
| Weight gain | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Weight loss | 3/119 (2.5%) | 4 | 9/181 (5%) | 9 |
| Metabolism and nutrition disorders | ||||
| Alkalosis | 2/119 (1.7%) | 2 | 0/181 (0%) | 0 |
| Anorexia | 16/119 (13.4%) | 18 | 32/181 (17.7%) | 36 |
| Blood bicarbonate decreased | 2/119 (1.7%) | 3 | 3/181 (1.7%) | 4 |
| Blood glucose increased | 56/119 (47.1%) | 75 | 79/181 (43.6%) | 122 |
| Blood uric acid increased | 2/119 (1.7%) | 2 | 9/181 (5%) | 12 |
| Dehydration | 5/119 (4.2%) | 5 | 7/181 (3.9%) | 7 |
| Glucose intolerance | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Renal tubular disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Serum albumin decreased | 36/119 (30.3%) | 41 | 40/181 (22.1%) | 63 |
| Serum calcium decreased | 37/119 (31.1%) | 45 | 52/181 (28.7%) | 75 |
| Serum calcium increased | 2/119 (1.7%) | 2 | 5/181 (2.8%) | 6 |
| Serum glucose decreased | 5/119 (4.2%) | 5 | 7/181 (3.9%) | 8 |
| Serum magnesium decreased | 12/119 (10.1%) | 13 | 28/181 (15.5%) | 33 |
| Serum magnesium increased | 3/119 (2.5%) | 3 | 19/181 (10.5%) | 19 |
| Serum phosphate decreased | 15/119 (12.6%) | 15 | 19/181 (10.5%) | 22 |
| Serum potassium decreased | 24/119 (20.2%) | 27 | 43/181 (23.8%) | 64 |
| Serum potassium increased | 6/119 (5%) | 6 | 9/181 (5%) | 12 |
| Serum sodium decreased | 23/119 (19.3%) | 27 | 35/181 (19.3%) | 44 |
| Serum sodium increased | 5/119 (4.2%) | 6 | 12/181 (6.6%) | 15 |
| Serum triglycerides increased | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Tumor lysis syndrome | 0/119 (0%) | 0 | 4/181 (2.2%) | 4 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/119 (1.7%) | 2 | 7/181 (3.9%) | 10 |
| Arthritis | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Back pain | 2/119 (1.7%) | 2 | 19/181 (10.5%) | 21 |
| Bone pain | 2/119 (1.7%) | 2 | 2/181 (1.1%) | 2 |
| Buttock pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Chest wall pain | 2/119 (1.7%) | 2 | 3/181 (1.7%) | 3 |
| Muscle weakness | 5/119 (4.2%) | 5 | 9/181 (5%) | 9 |
| Muscle weakness lower limb | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Musculoskeletal disorder | 0/119 (0%) | 0 | 6/181 (3.3%) | 6 |
| Myalgia | 4/119 (3.4%) | 5 | 6/181 (3.3%) | 7 |
| Neck pain | 2/119 (1.7%) | 2 | 1/181 (0.6%) | 1 |
| Pain in extremity | 7/119 (5.9%) | 7 | 9/181 (5%) | 9 |
| Trismus | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Nervous system disorders | ||||
| Acoustic nerve disorder NOS | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Ataxia | 5/119 (4.2%) | 6 | 2/181 (1.1%) | 2 |
| Cerebrospinal fluid leakage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Depressed level of consciousness | 2/119 (1.7%) | 2 | 5/181 (2.8%) | 6 |
| Dizziness | 10/119 (8.4%) | 11 | 12/181 (6.6%) | 13 |
| Dysgeusia | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 5 |
| Encephalopathy | 2/119 (1.7%) | 2 | 0/181 (0%) | 0 |
| Headache | 13/119 (10.9%) | 13 | 27/181 (14.9%) | 33 |
| Hypoglossal nerve disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Intracranial hemorrhage | 4/119 (3.4%) | 4 | 2/181 (1.1%) | 2 |
| Ischemia cerebrovascular | 3/119 (2.5%) | 3 | 3/181 (1.7%) | 3 |
| Leukoencephalopathy | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Memory impairment | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Mini mental status examination abnormal | 2/119 (1.7%) | 2 | 1/181 (0.6%) | 1 |
| Neuralgia | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 4 |
| Neurological disorder NOS | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Peripheral motor neuropathy | 5/119 (4.2%) | 6 | 8/181 (4.4%) | 10 |
| Peripheral sensory neuropathy | 15/119 (12.6%) | 16 | 26/181 (14.4%) | 36 |
| Seizure | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 5 |
| Sinus pain | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Speech disorder | 4/119 (3.4%) | 4 | 0/181 (0%) | 0 |
| Syncope | 3/119 (2.5%) | 3 | 5/181 (2.8%) | 5 |
| Tremor | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Trigeminal nerve disorder | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Psychiatric disorders | ||||
| Agitation | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Anxiety | 4/119 (3.4%) | 5 | 10/181 (5.5%) | 10 |
| Confusion | 6/119 (5%) | 6 | 10/181 (5.5%) | 11 |
| Depression | 3/119 (2.5%) | 3 | 9/181 (5%) | 10 |
| Euphoria | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Insomnia | 6/119 (5%) | 7 | 10/181 (5.5%) | 10 |
| Psychosis | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Renal and urinary disorders | ||||
| Bladder hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Bladder pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cystitis | 0/119 (0%) | 0 | 3/181 (1.7%) | 4 |
| Glomerular filtration rate decreased | 0/119 (0%) | 0 | 3/181 (1.7%) | 7 |
| Hemorrhage urinary tract | 2/119 (1.7%) | 2 | 3/181 (1.7%) | 4 |
| Proteinuria | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Renal failure | 6/119 (5%) | 6 | 7/181 (3.9%) | 12 |
| Ureteric hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Urethral pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Urinary frequency | 2/119 (1.7%) | 2 | 3/181 (1.7%) | 3 |
| Urinary incontinence | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Urinary retention | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Urine discoloration | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Urogenital disorder | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Reproductive system and breast disorders | ||||
| Irregular menstruation | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Vaginal hemorrhage | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Adult respiratory distress syndrome | 1/119 (0.8%) | 1 | 7/181 (3.9%) | 7 |
| Allergic rhinitis | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Apnea | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Aspiration | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Atelectasis | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 2 |
| Bronchial obstruction | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Bronchopulmonary hemorrhage | 1/119 (0.8%) | 2 | 0/181 (0%) | 0 |
| Bronchospasm | 2/119 (1.7%) | 3 | 3/181 (1.7%) | 5 |
| Cough | 10/119 (8.4%) | 11 | 21/181 (11.6%) | 25 |
| Dyspnea | 17/119 (14.3%) | 19 | 29/181 (16%) | 40 |
| Epistaxis | 7/119 (5.9%) | 7 | 3/181 (1.7%) | 3 |
| Hiccups | 0/119 (0%) | 0 | 5/181 (2.8%) | 5 |
| Hypoxia | 7/119 (5.9%) | 8 | 16/181 (8.8%) | 22 |
| Nasal congestion | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Pharyngeal examination abnormal | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Pharyngolaryngeal pain | 4/119 (3.4%) | 4 | 4/181 (2.2%) | 4 |
| Pleural effusion | 7/119 (5.9%) | 7 | 10/181 (5.5%) | 12 |
| Pleuritic pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Pneumonitis | 3/119 (2.5%) | 4 | 10/181 (5.5%) | 10 |
| Pneumothorax | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Pulmonary hemorrhage | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Respiratory disorder | 2/119 (1.7%) | 2 | 6/181 (3.3%) | 9 |
| Respiratory tract hemorrhage | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Voice alteration | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 5/119 (4.2%) | 5 | 14/181 (7.7%) | 16 |
| Decubitus ulcer | 0/119 (0%) | 0 | 7/181 (3.9%) | 8 |
| Dry skin | 0/119 (0%) | 0 | 3/181 (1.7%) | 4 |
| Nail disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Pain of skin | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Petechiae | 5/119 (4.2%) | 5 | 7/181 (3.9%) | 7 |
| Photosensitivity | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Pruritus | 3/119 (2.5%) | 3 | 7/181 (3.9%) | 8 |
| Rash acneiform | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Rash desquamating | 12/119 (10.1%) | 14 | 19/181 (10.5%) | 21 |
| Skin disorder | 3/119 (2.5%) | 3 | 3/181 (1.7%) | 3 |
| Skin hyperpigmentation | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Skin ulceration | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Sweating | 4/119 (3.4%) | 4 | 2/181 (1.1%) | 3 |
| Urticaria | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Vascular disorders | ||||
| Flushing | 2/119 (1.7%) | 2 | 0/181 (0%) | 0 |
| Hematoma | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Hemorrhage | 0/119 (0%) | 0 | 4/181 (2.2%) | 7 |
| Hypertension | 3/119 (2.5%) | 3 | 6/181 (3.3%) | 7 |
| Hypotension | 16/119 (13.4%) | 17 | 22/181 (12.2%) | 26 |
| Phlebitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Thrombosis | 2/119 (1.7%) | 2 | 13/181 (7.2%) | 13 |
| Vascular disorder | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 5 |
Other (Not Including Serious) Adverse Events |
||||
| Phase I - Alemtuzumab and Combination Chemotherapy | Phase II - Alemtuzumab and Combination Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 99/119 (83.2%) | 152/181 (84%) | ||
| Blood and lymphatic system disorders | ||||
| Bone marrow hypocellular | 2/119 (1.7%) | 2 | 0/181 (0%) | 0 |
| Disseminated intravascular coagulation | 7/119 (5.9%) | 7 | 11/181 (6.1%) | 11 |
| Febrile neutropenia | 55/119 (46.2%) | 74 | 93/181 (51.4%) | 141 |
| Hemoglobin decreased | 93/119 (78.2%) | 352 | 150/181 (82.9%) | 650 |
| Lymphatic disorder | 2/119 (1.7%) | 2 | 1/181 (0.6%) | 1 |
| Spleen disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cardiac disorders | ||||
| Arrhythmia | 3/119 (2.5%) | 3 | 1/181 (0.6%) | 1 |
| Atrial fibrillation | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 9 |
| Atrial flutter | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Atrial tachycardia | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cardiac disorder | 0/119 (0%) | 0 | 4/181 (2.2%) | 4 |
| Cardiac pain | 2/119 (1.7%) | 2 | 6/181 (3.3%) | 6 |
| Conduction disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Left ventricular dysfunction | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Left ventricular failure | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Myocardial ischemia | 0/119 (0%) | 0 | 0/181 (0%) | 0 |
| Palpitations | 0/119 (0%) | 0 | 3/181 (1.7%) | 7 |
| Pericardial effusion | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Restrictive cardiomyopathy | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 3 |
| Sinus bradycardia | 1/119 (0.8%) | 1 | 6/181 (3.3%) | 7 |
| Sinus tachycardia | 11/119 (9.2%) | 14 | 23/181 (12.7%) | 25 |
| Ventricular arrhythmia | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Ventricular fibrillation | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Ventricular tachycardia | 2/119 (1.7%) | 4 | 2/181 (1.1%) | 2 |
| Ear and labyrinth disorders | ||||
| Ear disorder | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Ear pain | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Hearing impaired | 0/119 (0%) | 0 | 5/181 (2.8%) | 5 |
| Middle ear inflammation | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Tinnitus | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Hyperthyroidism | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Eye disorders | ||||
| Conjunctivitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Diplopia | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Dry eye syndrome | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 11 |
| Eye disorder | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 5 |
| Eye pain | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Flashing vision | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Glaucoma | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Optic nerve edema | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Photophobia | 3/119 (2.5%) | 3 | 5/181 (2.8%) | 5 |
| Vision blurred | 3/119 (2.5%) | 3 | 13/181 (7.2%) | 15 |
| Vitreous hemorrhage | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Watering eyes | 2/119 (1.7%) | 2 | 3/181 (1.7%) | 3 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 6/119 (5%) | 6 | 4/181 (2.2%) | 4 |
| Abdominal pain | 14/119 (11.8%) | 18 | 45/181 (24.9%) | 57 |
| Anal exam abnormal | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Anal hemorrhage | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Anal pain | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Ascites | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Colitis | 3/119 (2.5%) | 3 | 3/181 (1.7%) | 3 |
| Constipation | 24/119 (20.2%) | 36 | 64/181 (35.4%) | 87 |
| Diarrhea | 47/119 (39.5%) | 63 | 80/181 (44.2%) | 124 |
| Dry mouth | 1/119 (0.8%) | 1 | 8/181 (4.4%) | 14 |
| Dyspepsia | 10/119 (8.4%) | 14 | 29/181 (16%) | 37 |
| Dysphagia | 7/119 (5.9%) | 7 | 10/181 (5.5%) | 10 |
| Ear, nose and throat examination abnormal | 22/119 (18.5%) | 27 | 48/181 (26.5%) | 60 |
| Esophageal mucositis | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Esophageal pain | 0/119 (0%) | 0 | 8/181 (4.4%) | 8 |
| Esophagitis | 6/119 (5%) | 6 | 3/181 (1.7%) | 3 |
| Flatulence | 1/119 (0.8%) | 2 | 3/181 (1.7%) | 3 |
| Gastric mucositis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Gastritis | 5/119 (4.2%) | 5 | 2/181 (1.1%) | 2 |
| Gastrointestinal disorder | 4/119 (3.4%) | 4 | 7/181 (3.9%) | 10 |
| Gastroscopy abnormal | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Gingival pain | 2/119 (1.7%) | 2 | 2/181 (1.1%) | 2 |
| Hemorrhoidal hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Hemorrhoids | 3/119 (2.5%) | 4 | 11/181 (6.1%) | 11 |
| Ileus | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Intra-abdominal hemorrhage | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Mucositis oral | 28/119 (23.5%) | 37 | 29/181 (16%) | 35 |
| Nausea | 59/119 (49.6%) | 112 | 121/181 (66.9%) | 287 |
| Oesophagoscopy abnormal | 0/119 (0%) | 0 | 4/181 (2.2%) | 4 |
| Oral hemorrhage | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Oral pain | 4/119 (3.4%) | 4 | 2/181 (1.1%) | 2 |
| Pancreatitis | 1/119 (0.8%) | 1 | 7/181 (3.9%) | 7 |
| Peritoneal pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Proctitis | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Rectal hemorrhage | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 5 |
| Rectal pain | 3/119 (2.5%) | 3 | 9/181 (5%) | 10 |
| Salivary gland disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Stomach pain | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 6 |
| Tooth disorder | 2/119 (1.7%) | 2 | 2/181 (1.1%) | 2 |
| Toothache | 4/119 (3.4%) | 4 | 4/181 (2.2%) | 4 |
| Upper gastrointestinal hemorrhage | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Vomiting | 32/119 (26.9%) | 54 | 78/181 (43.1%) | 142 |
| General disorders | ||||
| Chest pain | 4/119 (3.4%) | 5 | 9/181 (5%) | 10 |
| Chills | 19/119 (16%) | 20 | 46/181 (25.4%) | 65 |
| Death NOS | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Edema limbs | 17/119 (14.3%) | 27 | 49/181 (27.1%) | 78 |
| Facial pain | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Fatigue | 64/119 (53.8%) | 154 | 116/181 (64.1%) | 272 |
| Fever | 18/119 (15.1%) | 19 | 51/181 (28.2%) | 76 |
| Flu-like symptoms | 1/119 (0.8%) | 2 | 1/181 (0.6%) | 1 |
| Gait abnormal | 2/119 (1.7%) | 2 | 1/181 (0.6%) | 1 |
| General symptom | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 6 |
| Hypothermia | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Ill-defined disorder | 0/119 (0%) | 0 | 3/181 (1.7%) | 6 |
| Injection site reaction | 19/119 (16%) | 21 | 21/181 (11.6%) | 28 |
| Localized edema | 5/119 (4.2%) | 5 | 10/181 (5.5%) | 10 |
| Pain | 17/119 (14.3%) | 19 | 20/181 (11%) | 22 |
| Visceral edema | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Hepatobiliary disorders | ||||
| Hepatic failure | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Hepatobiliary disease | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Immune system disorders | ||||
| Hypersensitivity | 6/119 (5%) | 7 | 10/181 (5.5%) | 10 |
| Immune system disorder | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Infections and infestations | ||||
| Abdominal infection | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Anal infection | 2/119 (1.7%) | 2 | 5/181 (2.8%) | 6 |
| Anorectal infection | 2/119 (1.7%) | 3 | 8/181 (4.4%) | 11 |
| Bladder infection | 3/119 (2.5%) | 3 | 4/181 (2.2%) | 4 |
| Bronchitis | 2/119 (1.7%) | 2 | 3/181 (1.7%) | 3 |
| Catheter related infection | 16/119 (13.4%) | 20 | 18/181 (9.9%) | 21 |
| Conjunctivitis infective | 3/119 (2.5%) | 3 | 2/181 (1.1%) | 2 |
| Encephalitis infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Esophageal infection | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Eye infection | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Gingival infection | 3/119 (2.5%) | 3 | 7/181 (3.9%) | 7 |
| Ileal infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 2 |
| Infection | 13/119 (10.9%) | 15 | 16/181 (8.8%) | 20 |
| Infection with grade 3 or 4 neutropenia | 2/119 (1.7%) | 2 | 0/181 (0%) | 0 |
| Infection without neutropenia | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Infectious colitis | 4/119 (3.4%) | 5 | 7/181 (3.9%) | 8 |
| Laryngitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Lip infection | 4/119 (3.4%) | 5 | 3/181 (1.7%) | 4 |
| Mucosal infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Nail infection | 1/119 (0.8%) | 2 | 1/181 (0.6%) | 1 |
| Opportunistic infection | 2/119 (1.7%) | 5 | 3/181 (1.7%) | 3 |
| Otitis externa | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Otitis media | 2/119 (1.7%) | 2 | 3/181 (1.7%) | 3 |
| Paranasal sinus infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Penile infection | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 3 |
| Peripheral nerve infection | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Peritoneal infection | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Pharyngitis | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Phlebitis infective | 1/119 (0.8%) | 3 | 1/181 (0.6%) | 1 |
| Pneumonia | 10/119 (8.4%) | 12 | 16/181 (8.8%) | 20 |
| Rhinitis infective | 2/119 (1.7%) | 2 | 1/181 (0.6%) | 1 |
| Salivary gland infection | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Scrotal infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Sepsis | 28/119 (23.5%) | 39 | 54/181 (29.8%) | 64 |
| Sinusitis | 10/119 (8.4%) | 10 | 16/181 (8.8%) | 27 |
| Skin infection | 6/119 (5%) | 8 | 20/181 (11%) | 23 |
| Small intestine infection | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Soft tissue infection | 2/119 (1.7%) | 2 | 6/181 (3.3%) | 7 |
| Tooth infection | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Tracheitis | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Upper respiratory infection | 10/119 (8.4%) | 13 | 14/181 (7.7%) | 17 |
| Ureteritis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Urethral infection | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Urinary tract infection | 4/119 (3.4%) | 9 | 13/181 (7.2%) | 17 |
| Vaginal infection | 0/119 (0%) | 0 | 1/181 (0.6%) | 2 |
| Viral hepatitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Wound infection | 5/119 (4.2%) | 5 | 0/181 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Bruising | 1/119 (0.8%) | 1 | 5/181 (2.8%) | 7 |
| Dermatitis radiation | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Fracture | 0/119 (0%) | 0 | 2/181 (1.1%) | 3 |
| Intraoperative hepatobiliary injury - Gallbladder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Intraoperative venous injury - Vein-superior vena cava | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Postoperative hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Prolapse of intestinal stoma | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Vascular access complication | 2/119 (1.7%) | 2 | 6/181 (3.3%) | 6 |
| Wound dehiscence | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Investigations | ||||
| ADH abnormal | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Activated partial thromboplastin time prolonged | 24/119 (20.2%) | 38 | 39/181 (21.5%) | 64 |
| Alanine aminotransferase increased | 66/119 (55.5%) | 180 | 122/181 (67.4%) | 328 |
| Alkaline phosphatase | 1/119 (0.8%) | 2 | 0/181 (0%) | 0 |
| Alkaline phosphatase increased | 41/119 (34.5%) | 68 | 93/181 (51.4%) | 163 |
| Amylase increased | 4/119 (3.4%) | 4 | 9/181 (5%) | 12 |
| Aspartate aminotransferase increased | 59/119 (49.6%) | 137 | 108/181 (59.7%) | 266 |
| Blood bilirubin increased | 67/119 (56.3%) | 131 | 101/181 (55.8%) | 174 |
| Blood gonadotrophin abnormal | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| CD4 lymphocytes decreased | 0/119 (0%) | 0 | 2/181 (1.1%) | 5 |
| Carbon monoxide diffusing capacity decreased | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Cardiac troponin I increased | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cardiac troponin T increased | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Coagulopathy | 7/119 (5.9%) | 7 | 8/181 (4.4%) | 18 |
| Creatinine increased | 21/119 (17.6%) | 30 | 40/181 (22.1%) | 70 |
| Fibrinogen decreased | 57/119 (47.9%) | 66 | 93/181 (51.4%) | 118 |
| Forced expiratory volume decreased | 1/119 (0.8%) | 2 | 0/181 (0%) | 0 |
| Gamma-glutamyltransferase increased | 6/119 (5%) | 7 | 3/181 (1.7%) | 10 |
| INR increased | 8/119 (6.7%) | 10 | 25/181 (13.8%) | 48 |
| Laboratory test abnormal | 8/119 (6.7%) | 10 | 9/181 (5%) | 36 |
| Leukocyte count decreased | 19/119 (16%) | 45 | 43/181 (23.8%) | 123 |
| Lipase increased | 0/119 (0%) | 0 | 9/181 (5%) | 10 |
| Lymphocyte count decreased | 17/119 (14.3%) | 36 | 30/181 (16.6%) | 65 |
| Neutrophil count decreased | 95/119 (79.8%) | 312 | 147/181 (81.2%) | 575 |
| Platelet count decreased | 93/119 (78.2%) | 306 | 149/181 (82.3%) | 594 |
| Serum cholesterol increased | 3/119 (2.5%) | 3 | 2/181 (1.1%) | 2 |
| Vital capacity decreased | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Weight gain | 5/119 (4.2%) | 7 | 5/181 (2.8%) | 6 |
| Weight loss | 10/119 (8.4%) | 11 | 20/181 (11%) | 21 |
| Metabolism and nutrition disorders | ||||
| Alkalosis | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Anorexia | 20/119 (16.8%) | 27 | 54/181 (29.8%) | 80 |
| Blood bicarbonate decreased | 2/119 (1.7%) | 2 | 2/181 (1.1%) | 2 |
| Blood glucose increased | 91/119 (76.5%) | 281 | 137/181 (75.7%) | 426 |
| Blood uric acid increased | 9/119 (7.6%) | 10 | 15/181 (8.3%) | 25 |
| Dehydration | 3/119 (2.5%) | 4 | 9/181 (5%) | 10 |
| Iron overload | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Serum albumin decreased | 54/119 (45.4%) | 99 | 79/181 (43.6%) | 170 |
| Serum calcium decreased | 62/119 (52.1%) | 106 | 97/181 (53.6%) | 204 |
| Serum calcium increased | 3/119 (2.5%) | 10 | 7/181 (3.9%) | 8 |
| Serum glucose decreased | 8/119 (6.7%) | 11 | 20/181 (11%) | 34 |
| Serum magnesium decreased | 17/119 (14.3%) | 26 | 43/181 (23.8%) | 74 |
| Serum magnesium increased | 15/119 (12.6%) | 15 | 29/181 (16%) | 35 |
| Serum phosphate decreased | 19/119 (16%) | 28 | 39/181 (21.5%) | 47 |
| Serum potassium decreased | 40/119 (33.6%) | 78 | 89/181 (49.2%) | 184 |
| Serum potassium increased | 8/119 (6.7%) | 9 | 21/181 (11.6%) | 21 |
| Serum sodium decreased | 39/119 (32.8%) | 68 | 84/181 (46.4%) | 161 |
| Serum sodium increased | 5/119 (4.2%) | 6 | 8/181 (4.4%) | 9 |
| Serum triglycerides increased | 5/119 (4.2%) | 5 | 4/181 (2.2%) | 5 |
| Tumor lysis syndrome | 5/119 (4.2%) | 5 | 7/181 (3.9%) | 7 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 10/119 (8.4%) | 12 | 25/181 (13.8%) | 33 |
| Arthritis | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Back pain | 13/119 (10.9%) | 18 | 55/181 (30.4%) | 79 |
| Bone pain | 11/119 (9.2%) | 13 | 22/181 (12.2%) | 27 |
| Buttock pain | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Chest wall pain | 3/119 (2.5%) | 4 | 12/181 (6.6%) | 13 |
| Joint disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Joint range of motion decreased lumbar spine | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Muscle weakness | 7/119 (5.9%) | 9 | 15/181 (8.3%) | 32 |
| Muscle weakness lower limb | 2/119 (1.7%) | 2 | 6/181 (3.3%) | 6 |
| Muscle weakness upper limb | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Musculoskeletal disorder | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 5 |
| Myalgia | 12/119 (10.1%) | 15 | 26/181 (14.4%) | 36 |
| Neck pain | 1/119 (0.8%) | 1 | 11/181 (6.1%) | 16 |
| Osteonecrosis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Osteoporosis | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 4 |
| Pain in extremity | 8/119 (6.7%) | 9 | 26/181 (14.4%) | 38 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Myelodysplastic syndrome | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Treatment related secondary malignancy | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Nervous system disorders | ||||
| Acoustic nerve disorder NOS | 1/119 (0.8%) | 6 | 0/181 (0%) | 0 |
| Ataxia | 6/119 (5%) | 6 | 7/181 (3.9%) | 10 |
| Cerebrospinal fluid leakage | 2/119 (1.7%) | 3 | 1/181 (0.6%) | 1 |
| Cognitive disturbance | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Depressed level of consciousness | 2/119 (1.7%) | 2 | 2/181 (1.1%) | 2 |
| Dizziness | 19/119 (16%) | 27 | 38/181 (21%) | 51 |
| Dysgeusia | 8/119 (6.7%) | 9 | 11/181 (6.1%) | 12 |
| Encephalopathy | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Extrapyramidal disorder | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 3 |
| Facial nerve disorder | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Headache | 39/119 (32.8%) | 66 | 88/181 (48.6%) | 181 |
| Hydrocephalus | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Intracranial hemorrhage | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Ischemia cerebrovascular | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Leukoencephalopathy | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Memory impairment | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Mini mental status examination abnormal | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Myelitis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Neuralgia | 0/119 (0%) | 0 | 8/181 (4.4%) | 8 |
| Neurological disorder NOS | 0/119 (0%) | 0 | 8/181 (4.4%) | 10 |
| Peripheral motor neuropathy | 12/119 (10.1%) | 17 | 14/181 (7.7%) | 22 |
| Peripheral sensory neuropathy | 52/119 (43.7%) | 129 | 83/181 (45.9%) | 194 |
| Seizure | 0/119 (0%) | 0 | 1/181 (0.6%) | 2 |
| Sinus pain | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Speech disorder | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Syncope | 3/119 (2.5%) | 4 | 0/181 (0%) | 0 |
| Tremor | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Psychiatric disorders | ||||
| Agitation | 2/119 (1.7%) | 3 | 2/181 (1.1%) | 2 |
| Anxiety | 19/119 (16%) | 24 | 21/181 (11.6%) | 44 |
| Confusion | 5/119 (4.2%) | 5 | 8/181 (4.4%) | 8 |
| Depression | 20/119 (16.8%) | 22 | 26/181 (14.4%) | 46 |
| Insomnia | 15/119 (12.6%) | 27 | 31/181 (17.1%) | 48 |
| Libido decreased | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Personality change | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Psychosis | 0/119 (0%) | 0 | 5/181 (2.8%) | 5 |
| Renal and urinary disorders | ||||
| Bladder hemorrhage | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Bladder spasm | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Cystitis | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Glomerular filtration rate decreased | 0/119 (0%) | 0 | 3/181 (1.7%) | 7 |
| Hemoglobin urine positive | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Hemorrhage urinary tract | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Proteinuria | 2/119 (1.7%) | 2 | 4/181 (2.2%) | 6 |
| Renal failure | 3/119 (2.5%) | 3 | 6/181 (3.3%) | 9 |
| Urethral pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Urinary frequency | 5/119 (4.2%) | 5 | 13/181 (7.2%) | 14 |
| Urinary incontinence | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Urinary retention | 2/119 (1.7%) | 2 | 2/181 (1.1%) | 2 |
| Urine discoloration | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Urogenital disorder | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Reproductive system and breast disorders | ||||
| Breast pain | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Erectile dysfunction | 0/119 (0%) | 0 | 2/181 (1.1%) | 3 |
| Feminization | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Gynecomastia | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Ovulation pain | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Pelvic pain | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Testicular pain | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Vaginal dryness | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Vaginal hemorrhage | 4/119 (3.4%) | 4 | 4/181 (2.2%) | 5 |
| Vaginal mucositis | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Adult respiratory distress syndrome | 2/119 (1.7%) | 2 | 0/181 (0%) | 0 |
| Allergic rhinitis | 6/119 (5%) | 7 | 14/181 (7.7%) | 24 |
| Atelectasis | 2/119 (1.7%) | 3 | 1/181 (0.6%) | 1 |
| Bronchial hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Bronchial obstruction | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Bronchopulmonary hemorrhage | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Bronchospasm | 3/119 (2.5%) | 4 | 3/181 (1.7%) | 5 |
| Cough | 20/119 (16.8%) | 28 | 55/181 (30.4%) | 102 |
| Dyspnea | 21/119 (17.6%) | 37 | 48/181 (26.5%) | 74 |
| Dyspnea (shortness of breath) | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Epistaxis | 9/119 (7.6%) | 11 | 13/181 (7.2%) | 13 |
| Hiccups | 5/119 (4.2%) | 5 | 10/181 (5.5%) | 11 |
| Hypoxia | 5/119 (4.2%) | 5 | 9/181 (5%) | 10 |
| Laryngoscopy abnormal | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Nasal congestion | 0/119 (0%) | 0 | 3/181 (1.7%) | 3 |
| Pharyngeal examination abnormal | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Pharyngeal hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Pharyngeal mucositis | 1/119 (0.8%) | 1 | 2/181 (1.1%) | 2 |
| Pharyngolaryngeal pain | 5/119 (4.2%) | 5 | 18/181 (9.9%) | 21 |
| Pleural effusion | 6/119 (5%) | 6 | 11/181 (6.1%) | 12 |
| Pleuritic pain | 0/119 (0%) | 0 | 3/181 (1.7%) | 4 |
| Pneumonitis | 3/119 (2.5%) | 3 | 4/181 (2.2%) | 4 |
| Pulmonary hemorrhage | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Pulmonary hypertension | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Respiratory disorder | 1/119 (0.8%) | 1 | 9/181 (5%) | 12 |
| Respiratory tract hemorrhage | 0/119 (0%) | 0 | 1/181 (0.6%) | 1 |
| Tracheoscopy abnormal | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Voice alteration | 3/119 (2.5%) | 3 | 2/181 (1.1%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 24/119 (20.2%) | 49 | 33/181 (18.2%) | 57 |
| Decubitus ulcer | 0/119 (0%) | 0 | 2/181 (1.1%) | 2 |
| Dry skin | 2/119 (1.7%) | 2 | 7/181 (3.9%) | 12 |
| Hand-and-foot syndrome | 1/119 (0.8%) | 1 | 0/181 (0%) | 0 |
| Pain of skin | 1/119 (0.8%) | 1 | 1/181 (0.6%) | 1 |
| Petechiae | 8/119 (6.7%) | 9 | 15/181 (8.3%) | 16 |
| Photosensitivity | 1/119 (0.8%) | 2 | 3/181 (1.7%) | 7 |
| Pruritus | 5/119 (4.2%) | 6 | 23/181 (12.7%) | 26 |
| Rash acneiform | 4/119 (3.4%) | 5 | 3/181 (1.7%) | 4 |
| Rash desquamating | 29/119 (24.4%) | 37 | 65/181 (35.9%) | 97 |
| Skin disorder | 2/119 (1.7%) | 2 | 12/181 (6.6%) | 16 |
| Skin hyperpigmentation | 0/119 (0%) | 0 | 2/181 (1.1%) | 3 |
| Skin ulceration | 1/119 (0.8%) | 1 | 3/181 (1.7%) | 5 |
| Sweating | 9/119 (7.6%) | 10 | 31/181 (17.1%) | 36 |
| Urticaria | 1/119 (0.8%) | 1 | 6/181 (3.3%) | 7 |
| Vascular disorders | ||||
| Flushing | 2/119 (1.7%) | 2 | 3/181 (1.7%) | 3 |
| Hematoma | 1/119 (0.8%) | 1 | 4/181 (2.2%) | 4 |
| Hemorrhage | 2/119 (1.7%) | 2 | 9/181 (5%) | 9 |
| Hot flashes | 3/119 (2.5%) | 7 | 2/181 (1.1%) | 8 |
| Hypertension | 9/119 (7.6%) | 10 | 12/181 (6.6%) | 15 |
| Hypotension | 14/119 (11.8%) | 15 | 35/181 (19.3%) | 37 |
| Phlebitis | 3/119 (2.5%) | 3 | 4/181 (2.2%) | 4 |
| Thrombosis | 4/119 (3.4%) | 4 | 11/181 (6.1%) | 11 |
| Vascular disorder | 0/119 (0%) | 0 | 1/181 (0.6%) | 4 |
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 | Wendy Stock, M.D. |
|---|---|
| Organization | University of Chicago Medical Center |
| Phone | |
| wstock@medicin.bsd.uchicago.edu |
Responsible Party:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00061945
Other Study ID Numbers:
- NCI-2012-02807
- NCI-2012-02807
- CDR302482
- CALGB 10102
- CALGB-10102
- U10CA031946
First Posted:
Jun 6, 2003
Last Update Posted:
May 3, 2022
Last Verified:
Apr 1, 2022