Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Sponsor
Children's Oncology Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00557193
Collaborator
National Cancer Institute (NCI) (NIH)
218
170
3
1.3
Study Details
Study Description
Brief Summary
This phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- To estimate the 3-year event-free survival (EFS) of infants with mixed lineage leukemia-rearranged (MLL-R) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus the fms-related tyrosine kinase 3 (FLT3) inhibitor lestaurtinib.
SECONDARY OBJECTIVES:
-
To compare the 3-year EFS of infants with MLL-R ALL treated with chemotherapy plus the FLT3 inhibitor lestaurtinib to MLL-R patients treated with chemotherapy alone.
-
To determine a safe, tolerable and biologically active dose of lestaurtinib given in sequential combination with chemotherapy in MLL-R infants.
-
To characterize the pharmacokinetics and pharmacodynamics of lestaurtinib in infants when given at the proposed dose in sequential combination with chemotherapy.
-
To identify molecular mechanisms of resistance to lestaurtinib in leukemic blasts.
-
To describe levels of minimal residual disease in infants with ALL within the context of the proposed therapy, and correlate with outcome.
-
To identify gene expression patterns in diagnostic infant leukemia samples that correlate with outcome within the context of the proposed therapy.
-
To describe the outcome of infants with MLL-G ALL treated with a modified P9407 chemotherapy backbone that includes an extended continuation phase.
OUTLINE:
INDUCTION THERAPY (WEEKS 1-5): All patients receive induction therapy comprising vincristine sulfate intravenously (IV) over 1 minute on days 8, 15, 22, and 29; daunorubicin hydrochloride IV over 30 minutes on days 8 and 9; cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 (closed as of 05/19/09); pegaspargase or asparaginase intramuscularly (IM) on days 15, 18, 22, 25, 29, and 33; prednisone orally (PO) thrice daily (TID) or methylprednisolone IV on days 1-7; dexamethasone IV or PO TID on days 8-28; cytarabine IV over 30 minutes on days 8-21; methotrexate intrathecally (IT) on days 1 and 29; cytarabine IT on day 15; hydrocortisone IT on days 15 and 29; and filgrastim IV or subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Standard-risk patients are non-randomly assigned to receive a less intensive chemotherapy regimen without lestaurtinib (post-induction therapy A).
POST-INDUCTION THERAPY A: (for standard-risk patients MLL-germline [G])
INDUCTION INTENSIFICATION (WEEKS 6-9): Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on days 1 and 8; leucovorin calcium IV or PO every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is < 0.1 uM; cyclophosphamide IV over 30 minutes on days 15-19; etoposide IV over 2 hours on days 15-19; and filgrastim IV or SC beginning on day 20 and continuing until blood counts recover. Patients in morphologic remission proceed to re-induction therapy.
RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; daunorubicin hydrochloride IV over 30 minutes on days 1 and 2; cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4; pegaspargase or asparaginase IM on day 4; dexamethasone IV or PO twice daily (BID) on days 1-7 and 15-21; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on days 1 and 15; and filgrastim IV or SC beginning on day 5 and continuing until blood counts recover.
CONSOLIDATION (WEEKS 13-19): Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8; leucovorin calcium IV every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is < 0.1 uM; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on day 1; etoposide IV over 2 hours on days 15-19; cyclophosphamide IV over 30 minutes on days 15-19; high-dose cytarabine IV over 3 hours every 12 hours on days 29 and 30; pegaspargase or asparaginase IM on day 30; and filgrastim IV or SC beginning on day 20 and day 31 and continuing until blood counts recover.
CONTINUATION I (WEEKS 20-41): Patients receive vincristine sulfate IV on day 1 in weeks 20 and 24; dexamethasone IV or PO BID on days 1-5 in weeks 20, and 24; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on day 1 in weeks 20 and 24; methotrexate IV on day 1 in weeks 21-24 and 25-27; etoposide IV over 2 hours on day 1-5 in week 28; cyclophosphamide IV over 30 minutes on days 1-5 in week 28; mercaptopurine PO on days 1-7 in weeks 21-23 and 25-27; and filgrastim SC or IV beginning on day 6 in week 28 and continuing until blood counts recover.
CONTINUATION II (WEEKS 42-104): Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone IV or PO BID on days 1-5, 29-33, and 57-61; methotrexate IT on day 1; methotrexate PO on days 8, 15, 22, 36, 43, 50, 64, 71, and 78; and mercaptopurine PO on days 8-28, 36-56, and 64-84. Treatment repeats every 12 weeks for 2 years from diagnosis.
A safety/activity phase is conducted separately for the intermediate-risk (IR) and high-risk (HR) patients to identify a safe, tolerable, and biologically active dose of lestaurtinib combined with chemotherapy backbone. Once a tolerable/active dose of lestaurtinib has been identified for IR patients, subsequent IR patients are eligible to proceed to an efficacy phase, where they are randomized (or non-randomly assigned as of 7/16/2014) to chemotherapy with or without lestaurtinib. HR patients separately proceed to the randomized efficacy phase if a tolerable/active dose is identified for the HR stratum. IR and HR patients are randomized (or non-randomly assigned as of 7/16/2014) to 1 of 2 post-induction therapy regimens (post-induction therapy B or C).
POST-INDUCTION THERAPY B: (chemotherapy only for IR/HR patients classified as MLL-R; age >= 90 days at diagnosis):
INDUCTION INTENSIFICATION (WEEKS 6-9): Patients receive high-dose methotrexate, leucovorin calcium, cyclophosphamide, etoposide, and filgrastim as in post-induction therapy A induction intensification. Patients in morphologic remission proceed to re-induction. (Retired as of 7/16/2014)
RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, pegaspargase or asparaginase, dexamethasone, triple IT chemotherapy, and filgrastim as in post-induction therapy A re-induction. (Retired as of 7/16/2014)
CONSOLIDATION (WEEKS 13-19): Patients receive high-dose methotrexate, leucovorin calcium, triple IT chemotherapy, etoposide, cyclophosphamide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy A consolidation. (Retired as of 7/16/2014)
CONTINUATION I (WEEKS 20-49): Patients receive vincristine sulfate IV over 1 minute on day 1 in weeks 20, 24, 33, 37, and 46; dexamethasone PO or IV BID on days 1-5 in weeks 20, 24, 33, 37, and 46; triple IT chemotherapy on day 1 in weeks 20, 24, 33, 37, and 46; methotrexate IV on day 1 in weeks 21-23, 25-26 and 37-45; mercaptopurine PO on days 1-7 in weeks 21-23, 25-26 and 37-45; etoposide IV over 2 hours on days 1-5 in week 27; cyclophosphamide IV over 2 hours on days 1-5 in week 27: high-dose cytarabine IV over 3 hours every 12 hours on days 1 and 2 in week 30; pegaspargase or asparaginase IM on day 2 in week 30: and filgrastim SC or IV beginning on day 3 in weeks 30 and continuing until blood counts recover. (Retired as of 7/16/2014)
CONTINUATION II (WEEKS 50-104): Patients receive vincristine sulfate, dexamethasone, IT methotrexate, methotrexate PO, and mercaptopurine PO as in post-induction therapy A continuation II. Treatment repeats every 12 weeks for 2 years from diagnosis. (Retired as of 7/16/2014)
POST-INDUCTION THERAPY C: (chemotherapy and lestaurtinib for IR/HR patients classified as MLL-R; age < 90 days at diagnosis)
INDUCTION INTENSIFICATION THERAPY (WEEKS 6-9): Patients receive high-dose methotrexate, leucovorin calcium, cyclophosphamide, etoposide, and filgrastim as in post-induction therapy B induction intensification. Patients also receive lestaurtinib PO BID on days 20-27. Patients in morphologic remission proceed to re-induction.
RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, pegaspargase or asparaginase, dexamethasone, triple IT chemotherapy, and filgrastim as in post-induction therapy B re-induction. Patients also receive lestaurtinib PO on days 5-20.
CONSOLIDATION (WEEKS 13-19) Patients receive high-dose methotrexate, leucovorin calcium, triple IT chemotherapy, etoposide, cyclophosphamide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy B consolidation. Patients also receive lestaurtinib PO on days 20-27 and 31-42.
CONTINUATION I (WEEKS 20-49): Patients receive vincristine sulfate, dexamethasone, triple IT chemotherapy, methotrexate, mercaptopurine, etoposide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy B continuation I. Patients also receive lestaurtinib PO on days 2-6 in weeks 20 and 24; days 27-41 in weeks 27-29; days 45-56 in weeks 30-32.
CONTINUATION II (WEEKS 50-104): Patients receive vincristine sulfate, dexamethasone, IT methotrexate, methotrexate PO, and mercaptopurine PO as in post-induction therapy B continuation II. Treatment repeats every 12 weeks for 2 years from diagnosis.
After completion of study treatment, all patients are followed up every 1-6 months for 4 years and then annually thereafter.
Study Design
Study Type:
Interventional
Actual Enrollment
:
218 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807)
Actual Study Start Date
:
Jan 14, 2008
Actual Primary Completion Date
:
Sep 30, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A (standard risk MLL-G) Population Description: Eligible patients with MLL-G (germline, or non-rearranged) |
Drug: Asparaginase
Given IV, IM, or PO
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Etoposide
Given IV
Other Names:
Biological: Filgrastim
Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IV, IT, or PO
Other Names:
Drug: Methylprednisolone
Given IV
Other Names:
Drug: Pegaspargase
Given IM
Other Names:
Other: Pharmacological Study
Correlative studies
Drug: Prednisone
Given PO
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Arm B (IR/HR MLL-R chemotherapy) Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. |
Drug: Asparaginase
Given IV, IM, or PO
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Etoposide
Given IV
Other Names:
Biological: Filgrastim
Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IV, IT, or PO
Other Names:
Drug: Methylprednisolone
Given IV
Other Names:
Drug: Pegaspargase
Given IM
Other Names:
Other: Pharmacological Study
Correlative studies
Drug: Prednisone
Given PO
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Experimental: Arm C (IR/HR MLL-R chemotherapy and lestaurtinib) Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. |
Drug: Asparaginase
Given IV, IM, or PO
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Etoposide
Given IV
Other Names:
Biological: Filgrastim
Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lestaurtinib
Given PO
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IV, IT, or PO
Other Names:
Drug: Methylprednisolone
Given IV
Other Names:
Drug: Pegaspargase
Given IM
Other Names:
Other: Pharmacological Study
Correlative studies
Drug: Prednisone
Given PO
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2) [From start of post-induction therapy for up to 10 years]
EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Secondary Outcome Measures
- Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2 [From start of post-induction therapy for up to 10 years.]
Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. EFS will be compared between patients on treatment Arm C at DL2 to those on Arm B.
- Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT) [Up to 12 weeks from start of induction]
Lestaurtinib-related dose-limiting toxicity proportions, as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, will by summarized by dose level for Safety phase patients.
- Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [Up to 12 weeks]
Pharmacokinetic AGP levels in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
- Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [Up to 12 weeks]
Pharmacokinetic albumin in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
- Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [Sampled between weeks 6-12 from start of induction]
Summarized with mean and standard deviation for those with available data in Arm C
- Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts [Sampled at the start of induction]
Described via mean and standard deviation by group.
- Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts [At relapse (up to 3 years)]
Described via means and standard deviations in available Arm C relapse samples
- Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts [Sampled at the start of induction]
Described via means and standard deviations in samples which have primary resistance to lestaurtinib
- Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts [At relapse (up to 3 years)]
Described via means and standard deviations in samples which have acquired resistance to lestaurtinib
- Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm [3 Years from end of Induction)]
Three-year EFS estimates and 90% CI will be reported by treatment arm and end-induction MRD status.
- Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With Survival Outcomes [At 3 years]
EFS outcomes will be reported by genotype.
- Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With PIA Values [At 3 years]
Means and standard deviations of Plasma Inhibitory Activity (PIA) will be given by genotype
- Percent Probability for Event-free Survival (EFS) for Patients on Arm A [From start of post-induction therapy for up to 10 years]
EFS time is defined as time from treatment assignment to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
to 1 Year
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients must be enrolled on a Children's Oncology Group (COG) ALL Classification Study (AALL08B1) prior to enrollment on AALL0631
-
Patients must be newly diagnosed with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL); patients with T-cell ALL are eligible; patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominately lymphoid
-
Patients with mature B-cell ALL or acute myelogenous leukemia (AML) are NOT eligible
-
Patients with Down syndrome are NOT eligible
-
Patients must be previously untreated with the exception of steroids and intrathecal chemotherapy; no other systemic chemotherapy may have been administered; patients receiving prior steroid therapy are eligible for study; any amount of steroid pretreatment will not affect initial induction assignment as long as the patient meets all other eligibility criteria; IT chemotherapy per protocol is allowed for patient convenience at the time of the diagnostic bone marrow or venous line placement to avoid second lumbar puncture; (note: the central nervous system [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
-
All patients and/or their parents or legal guardians must sign a written informed consent
-
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
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 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
| 4 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202-3591 |
| 5 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 6 | Kaiser Permanente Downey Medical Center | Downey | California | United States | 90242 |
| 7 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
| 8 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
| 9 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 10 | Children's Hospital Central California | Madera | California | United States | 93636-8762 |
| 11 | Children's Hospital and Research Center at Oakland | Oakland | California | United States | 94609-1809 |
| 12 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
| 13 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
| 14 | Lucile Packard Children's Hospital Stanford University | Palo Alto | California | United States | 94304 |
| 15 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 16 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
| 17 | UCSF Medical Center-Parnassus | San Francisco | California | United States | 94143 |
| 18 | UCSF Medical Center-Mission Bay | San Francisco | California | United States | 94158 |
| 19 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 20 | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | United States | 80218 |
| 21 | Connecticut Children's Medical Center | Hartford | Connecticut | United States | 06106 |
| 22 | Yale University | New Haven | Connecticut | United States | 06520 |
| 23 | Alfred I duPont Hospital for Children | Wilmington | Delaware | United States | 19803 |
| 24 | MedStar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
| 25 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 26 | Lee Memorial Health System | Fort Myers | Florida | United States | 33901 |
| 27 | Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | United States | 33908 |
| 28 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
| 29 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
| 30 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
| 31 | Miami Cancer Institute | Miami | Florida | United States | 33176 |
| 32 | Florida Hospital Orlando | Orlando | Florida | United States | 32803 |
| 33 | Arnold Palmer Hospital for Children | Orlando | Florida | United States | 32806 |
| 34 | Nemours Children's Clinic - Orlando | Orlando | Florida | United States | 32806 |
| 35 | UF Cancer Center at Orlando Health | Orlando | Florida | United States | 32806 |
| 36 | Nemours Children's Hospital | Orlando | Florida | United States | 32827 |
| 37 | Nemours Children's Clinic - Pensacola | Pensacola | Florida | United States | 32504 |
| 38 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
| 39 | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | United States | 33607 |
| 40 | Saint Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
| 41 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
| 42 | Augusta University Medical Center | Augusta | Georgia | United States | 30912 |
| 43 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
| 44 | University of Hawaii Cancer Center | Honolulu | Hawaii | United States | 96813 |
| 45 | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | United States | 96826 |
| 46 | Tripler Army Medical Center | Honolulu | Hawaii | United States | 96859 |
| 47 | Saint Luke's Mountain States Tumor Institute | Boise | Idaho | United States | 83712 |
| 48 | Lurie Children's Hospital-Chicago | Chicago | Illinois | United States | 60611 |
| 49 | University of Illinois | Chicago | Illinois | United States | 60612 |
| 50 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
| 51 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 52 | Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | United States | 60453 |
| 53 | Advocate Children's Hospital-Park Ridge | Park Ridge | Illinois | United States | 60068 |
| 54 | Advocate Lutheran General Hospital | Park Ridge | Illinois | United States | 60068 |
| 55 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
| 56 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
| 57 | Blank Children's Hospital | Des Moines | Iowa | United States | 50309 |
| 58 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
| 59 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
| 60 | Tulane University Health Sciences Center | New Orleans | Louisiana | United States | 70112 |
| 61 | Children's Hospital New Orleans | New Orleans | Louisiana | United States | 70118 |
| 62 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
| 63 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
| 64 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
| 65 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 66 | Floating Hospital for Children at Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
| 67 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
| 68 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 69 | Michigan State University Clinical Center | East Lansing | Michigan | United States | 48824-7016 |
| 70 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
| 71 | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | United States | 49503 |
| 72 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
| 73 | Kalamazoo Center for Medical Studies | Kalamazoo | Michigan | United States | 49008 |
| 74 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
| 75 | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
| 76 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 77 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
| 78 | Columbia Regional | Columbia | Missouri | United States | 65201 |
| 79 | The Childrens Mercy Hospital | Kansas City | Missouri | United States | 64108 |
| 80 | Mercy Hospital Saint Louis | Saint Louis | Missouri | United States | 63141 |
| 81 | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | United States | 68114 |
| 82 | Nevada Cancer Research Foundation CCOP | Las Vegas | Nevada | United States | 89106 |
| 83 | Children's Specialty Center of Nevada II | Las Vegas | Nevada | United States | 89109 |
| 84 | Summerlin Hospital Medical Center | Las Vegas | Nevada | United States | 89144 |
| 85 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 86 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 87 | Saint Barnabas Medical Center | Livingston | New Jersey | United States | 07039 |
| 88 | Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
| 89 | Saint Peter's University Hospital | New Brunswick | New Jersey | United States | 08901 |
| 90 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
| 91 | Newark Beth Israel Medical Center | Newark | New Jersey | United States | 07112 |
| 92 | Saint Joseph's Regional Medical Center | Paterson | New Jersey | United States | 07503 |
| 93 | Overlook Hospital | Summit | New Jersey | United States | 07902 |
| 94 | University of New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87102 |
| 95 | Albany Medical Center | Albany | New York | United States | 12208 |
| 96 | Montefiore Medical Center - Moses Campus | Bronx | New York | United States | 10467 |
| 97 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 98 | NYU Winthrop Hospital | Mineola | New York | United States | 11501 |
| 99 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
| 100 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
| 101 | University of Rochester | Rochester | New York | United States | 14642 |
| 102 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
| 103 | New York Medical College | Valhalla | New York | United States | 10595 |
| 104 | Mission Hospital Inc-Memorial Campus | Asheville | North Carolina | United States | 28801 |
| 105 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
| 106 | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | United States | 28203 |
| 107 | Novant Health Presbyterian Medical Center | Charlotte | North Carolina | United States | 28204 |
| 108 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 109 | East Carolina University | Greenville | North Carolina | United States | 27834 |
| 110 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 111 | Sanford Broadway Medical Center | Fargo | North Dakota | United States | 58122 |
| 112 | Children's Hospital Medical Center of Akron | Akron | Ohio | United States | 44308 |
| 113 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 114 | Rainbow Babies and Childrens Hospital | Cleveland | Ohio | United States | 44106 |
| 115 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 116 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 117 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
| 118 | The Toledo Hospital/Toledo Children's Hospital | Toledo | Ohio | United States | 43606 |
| 119 | Mercy Children's Hospital | Toledo | Ohio | United States | 43608 |
| 120 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 121 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
| 122 | Legacy Emanuel Hospital and Health Center | Portland | Oregon | United States | 97227 |
| 123 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
| 124 | Penn State Children's Hospital | Hershey | Pennsylvania | United States | 17033 |
| 125 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 126 | Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania | United States | 19134 |
| 127 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
| 128 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
| 129 | Palmetto Health Richland | Columbia | South Carolina | United States | 29203 |
| 130 | BI-LO Charities Children's Cancer Center | Greenville | South Carolina | United States | 29605 |
| 131 | Greenville Cancer Treatment Center | Greenville | South Carolina | United States | 29605 |
| 132 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
| 133 | East Tennessee Childrens Hospital | Knoxville | Tennessee | United States | 37916 |
| 134 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 135 | Texas Tech University Health Sciences Center-Amarillo | Amarillo | Texas | United States | 79106 |
| 136 | Dell Children's Medical Center of Central Texas | Austin | Texas | United States | 78723 |
| 137 | Driscoll Children's Hospital | Corpus Christi | Texas | United States | 78411 |
| 138 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 139 | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | United States | 75390 |
| 140 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 141 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
| 142 | Covenant Children's Hospital | Lubbock | Texas | United States | 79410 |
| 143 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
| 144 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
| 145 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
| 146 | Primary Children's Hospital | Salt Lake City | Utah | United States | 84113 |
| 147 | University of Vermont College of Medicine | Burlington | Vermont | United States | 05405 |
| 148 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22042 |
| 149 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
| 150 | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | United States | 99204 |
| 151 | Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | United States | 98405 |
| 152 | Madigan Army Medical Center | Tacoma | Washington | United States | 98431 |
| 153 | West Virginia University Charleston Division | Charleston | West Virginia | United States | 25304 |
| 154 | Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin | United States | 54301 |
| 155 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
| 156 | Marshfield Clinic | Marshfield | Wisconsin | United States | 54449 |
| 157 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 158 | Princess Margaret Hospital for Children | Perth | Western Australia | Australia | 6008 |
| 159 | Alberta Children's Hospital | Calgary | Alberta | Canada | T3B 6A8 |
| 160 | University of Alberta Hospital | Edmonton | Alberta | Canada | T6G 2B7 |
| 161 | British Columbia Children's Hospital | Vancouver | British Columbia | Canada | V6H 3V4 |
| 162 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 163 | Janeway Child Health Centre | Saint John's | Newfoundland and Labrador | Canada | A1B 3V6 |
| 164 | IWK Health Centre | Halifax | Nova Scotia | Canada | B3K 6R8 |
| 165 | Children's Hospital | London | Ontario | Canada | N6A 5W9 |
| 166 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
| 167 | Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
| 168 | The Montreal Children's Hospital of the MUHC | Montreal | Quebec | Canada | H3H 1P3 |
| 169 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
| 170 | Starship Children's Hospital | Grafton | Auckland | New Zealand | 1145 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Joanne Hilden, Children's Oncology Group
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00557193
Other Study ID Numbers:
- AALL0631
- NCI-2009-00313
- COG-AALL0631
- 08-146
- CDR0000573996
- AALL0631
- AALL0631
- U10CA180886
- U10CA098543
First Posted:
Nov 12, 2007
Last Update Posted:
Mar 25, 2022
Last Verified:
Mar 1, 2022
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Infants with Acute Lymphoblastic Leukemia (ALL) |
|---|---|
| Pre-assignment Detail | MLL-germline [G] to SR (Arm A/Group 1), MLL-rearranged [R] randomized/assigned to Arm B (Group2; chemo) or Arm C (Group3; chemo+lestaurtinib) with dose determined by age at dx (>=90 days is IR and <90 days is HR) |
| Arm/Group Title | Induction (All Patients) | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (Safety/ Dose Level 1) | ARM C (Safety/ Dose Level 2) | Arm C (Efficacy/ Dose Level 2) |
|---|---|---|---|---|---|---|
| Arm/Group Description | All Patients for Induction (not assigned). | Eligible patients with MLL-G (germline, or non-rearranged) Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 1 (DL1) (HR: 3.5 mg/kg/day; SR: 4 mg/kg/day) | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2) (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2)-Efficacy (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) |
| Period Title: Induction | ||||||
| STARTED | 218 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 192 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 26 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Induction | ||||||
| STARTED | 0 | 60 | 54 | 11 | 11 | 56 |
| COMPLETED | 0 | 50 | 22 | 4 | 4 | 19 |
| NOT COMPLETED | 0 | 10 | 32 | 7 | 7 | 37 |
Baseline Characteristics
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | All patients for Induction |
| Overall Participants | 218 |
| Age (Count of Participants) | |
| <=18 years |
218
100%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
0
0%
|
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
0.54
(0.28)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
122
56%
|
| Male |
96
44%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
50
22.9%
|
| Not Hispanic or Latino |
160
73.4%
|
| Unknown or Not Reported |
8
3.7%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
3
1.4%
|
| Asian |
9
4.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
16
7.3%
|
| White |
167
76.6%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
23
10.6%
|
| Region of Enrollment (Count of Participants) | |
| United States |
201
92.2%
|
| Canada |
15
6.9%
|
| New Zealand |
1
0.5%
|
| Australia |
1
0.5%
|
Outcome Measures
| Title | Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2) |
|---|---|
| Description | EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. |
| Time Frame | From start of post-induction therapy for up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 67 patients on Arm C (Safety and Efficacy at Dose Level 2) were included in the analysis. |
| Arm/Group Title | Arm C (Safety/Efficacy Dose Level 2) |
|---|---|
| Arm/Group Description | Arm C (Safety and Efficacy), IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) |
| Measure Participants | 67 |
| Number (90% Confidence Interval) [percentage probability] |
35.82
|
| Title | Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2 |
|---|---|
| Description | Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. EFS will be compared between patients on treatment Arm C at DL2 to those on Arm B. |
| Time Frame | From start of post-induction therapy for up to 10 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All eligible Arm B and ARM C (Dose Level 2) patients were included in the analysis. |
| Arm/Group Title | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|---|
| Arm/Group Description | Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 54 | 67 |
| Number (90% Confidence Interval) [percent probability] |
38.89
|
35.82
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm C (Safety/Efficacy Dose Level 2), Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|---|
| Comments | A one-sided log rank test will be used for testing whether the EFS in Arm C (chemo+lest) at DL2 is greater than the EFS in Arm B (chemo). This is equivalent to testing the null hypothesis of hazard ratio (HR)=1 versus the alternative of HR<1. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.672 |
| Comments | A priori significance level threshold of alpha=0.15 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.107 | |
| Confidence Interval |
(1-Sided) 85% to 1.403 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Arm C is the numerator and Arm B is the denominator of the estimated hazard ratio | |
| Title | Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT) |
|---|---|
| Description | Lestaurtinib-related dose-limiting toxicity proportions, as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, will by summarized by dose level for Safety phase patients. |
| Time Frame | Up to 12 weeks from start of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Arm C patients of Safety Phase who were evaluable for DLT. The first 10 evaluable patients enrolled on each dose level were included for monitoring dose limiting toxicity. |
| Arm/Group Title | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 1) | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 2) |
|---|---|---|
| Arm/Group Description | Evaluable Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at DL1 (HR: 3.5 mg/kg/day; SR: 4 mg/kg/day) | Evaluable Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) |
| Measure Participants | 10 | 10 |
| Count of Participants [Participants] |
0
0%
|
1
NaN
|
| Title | Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy |
|---|---|
| Description | Pharmacokinetic AGP levels in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data. |
| Time Frame | Up to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was and never will be collected |
| Arm/Group Title | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|
| Arm/Group Description | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 0 |
| Title | Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy |
|---|---|
| Description | Pharmacokinetic albumin in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data. |
| Time Frame | Up to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was and never will be collected |
| Arm/Group Title | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|
| Arm/Group Description | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 0 |
| Title | Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy |
|---|---|
| Description | Summarized with mean and standard deviation for those with available data in Arm C |
| Time Frame | Sampled between weeks 6-12 from start of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Arm C Dose Level 2 (DL2) patients who had data available for analysis. |
| Arm/Group Title | Arm C (Safety/Efficacy Dose Level 2) |
|---|---|
| Arm/Group Description | Arm C (Safety and Efficacy), IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) |
| Measure Participants | 63 |
| Mean (Standard Deviation) [Activity percentage] |
69.00
(22.96)
|
| Title | Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts |
|---|---|
| Description | Described via mean and standard deviation by group. |
| Time Frame | Sampled at the start of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients who had data collected |
| Arm/Group Title | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|---|---|
| Arm/Group Description | Population Description: Eligible patients with MLL-G (germline, or non-rearranged) Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 51 | 38 | 65 |
| Mean (Standard Deviation) [qPCR fold expression ratio] |
1.25
(2.12)
|
7.85
(10.65)
|
5.83
(5.55)
|
| Title | Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts |
|---|---|
| Description | Described via means and standard deviations in available Arm C relapse samples |
| Time Frame | At relapse (up to 3 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Arm C Dose Level 2 patients who relapsed and had data collected. |
| Arm/Group Title | Arm C (Safety/Efficacy Dose Level 2) |
|---|---|
| Arm/Group Description | Arm C (Safety and Efficacy), IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) |
| Measure Participants | 7 |
| Mean (Standard Deviation) [qPCR fold expression ratio] |
5.73
(4.56)
|
| Title | Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts |
|---|---|
| Description | Described via means and standard deviations in samples which have primary resistance to lestaurtinib |
| Time Frame | Sampled at the start of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients who had data collected |
| Arm/Group Title | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|---|---|
| Arm/Group Description | Population Description: Eligible patients with MLL-G (germline, or non-rearranged) Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 43 | 37 | 62 |
| Median (Standard Deviation) [Proportion of cells that are viable] |
0.75
(0.14)
|
0.48
(0.19)
|
0.47
(0.19)
|
| Title | Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts |
|---|---|
| Description | Described via means and standard deviations in samples which have acquired resistance to lestaurtinib |
| Time Frame | At relapse (up to 3 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Arm C Dose Level 2 patients who relapsed and had data collected |
| Arm/Group Title | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|
| Arm/Group Description | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 7 |
| Mean (Standard Deviation) [Proportion of cells that are viable] |
0.69
(0.15)
|
| Title | Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm |
|---|---|
| Description | Three-year EFS estimates and 90% CI will be reported by treatment arm and end-induction MRD status. |
| Time Frame | 3 Years from end of Induction) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients who had data collected |
| Arm/Group Title | Arm A (MRD Negative) | Arm A (MRD Positive) | Arm B (MRD Negative) | Arm B (MRD Positive) | Arm C (MRD Negative) | Arm C (MRD Positive) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Arm A, standard risk MLL-G | Arm A, standard risk MLL-G | Arm B, IR/HR MLL-R chemotherapy | Arm B, IR/HR MLL-R chemotherapy | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib |
| Measure Participants | 43 | 8 | 19 | 22 | 27 | 37 |
| Number (90% Confidence Interval) [percent probability] |
86.05
|
87.5
|
47.37
|
22.73
|
51.85
|
27.03
|
| Title | Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With Survival Outcomes |
|---|---|
| Description | EFS outcomes will be reported by genotype. |
| Time Frame | At 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was and never will never be collected. |
| Arm/Group Title | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|---|---|
| Arm/Group Description | Population Description: Eligible patients with MLL-G (germline, or non-rearranged) Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 0 | 0 | 0 |
| Title | Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With PIA Values |
|---|---|
| Description | Means and standard deviations of Plasma Inhibitory Activity (PIA) will be given by genotype |
| Time Frame | At 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was and never will be collected |
| Arm/Group Title | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) |
|---|---|---|---|
| Arm/Group Description | Population Description: Eligible patients with MLL-G (germline, or non-rearranged) Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Lestaurtinib: Given PO Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 0 | 0 | 0 |
| Title | Percent Probability for Event-free Survival (EFS) for Patients on Arm A |
|---|---|
| Description | EFS time is defined as time from treatment assignment to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. |
| Time Frame | From start of post-induction therapy for up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Eligible patients treated in Arm A (standard risk MLL-G). |
| Arm/Group Title | Arm A (Standard Risk MLL-G) |
|---|---|
| Arm/Group Description | Eligible patients with MLL-G (germline, or non-rearranged) Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV |
| Measure Participants | 60 |
| Number (90% Confidence Interval) [percentage probability] |
86.67
|
Adverse Events
| Time Frame | Group 1: Study Entry to end-Induction (5 weeks). Other Groups: Start of Induction Intensification (Week 6) through 10 years post study enrollment. | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events. | |||||||||||||
| Arm/Group Title | Induction (All Patients) | Post Induction (Follow-up Only) | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (Safety/ Dose Level 1) | Arm C (Safety/ Dose Level 2) | Arm C (Efficacy/ Dose Level 2) | |||||||
| Arm/Group Description | All Patients for Induction (not assigned) | Post-Induction patients that did not receive therapy | Population Description: Eligible patients with MLL-G (germline, or non-rearranged) Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis. Asparaginase: Given IV, IM, or PO Cyclophosphamide: Given IV Cytarabine: Given IV or IT Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IV, IT, or PO Methylprednisolone: Given IV Pegaspargase: Given IM Pharmacological Study: Correlative studies Prednisone: Given PO Therapeutic Hydrocortisone: Given IT Vincristine Sulfate: Given IV | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 1 (DL1) (HR: 3.5 mg/kg/day; SR: 4 mg/kg/day) | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2) (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) | Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2)-Efficacy (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) | |||||||
All Cause Mortality |
||||||||||||||
| Induction (All Patients) | Post Induction (Follow-up Only) | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (Safety/ Dose Level 1) | Arm C (Safety/ Dose Level 2) | Arm C (Efficacy/ Dose Level 2) | ||||||||
| 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 | 6/210 (2.9%) | 6/12 (50%) | 3/60 (5%) | 31/54 (57.4%) | 6/11 (54.5%) | 5/11 (45.5%) | 28/56 (50%) | |||||||
Serious Adverse Events |
||||||||||||||
| Induction (All Patients) | Post Induction (Follow-up Only) | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (Safety/ Dose Level 1) | Arm C (Safety/ Dose Level 2) | Arm C (Efficacy/ Dose Level 2) | ||||||||
| 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 | 9/210 (4.3%) | 0/12 (0%) | 2/60 (3.3%) | 9/54 (16.7%) | 8/11 (72.7%) | 7/11 (63.6%) | 41/56 (73.2%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 2/56 (3.6%) | 5 |
| Blood and lymphatic system disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Febrile neutropenia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 6/11 (54.5%) | 7 | 1/11 (9.1%) | 1 | 22/56 (39.3%) | 42 |
| Hemolytic uremic syndrome | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Thrombotic thrombocytopenic purpura | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Cardiac disorders | ||||||||||||||
| Cardiac arrest | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 1 |
| Heart failure | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Left ventricular systolic dysfunction | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Myocarditis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Sinus tachycardia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 3 |
| Gastrointestinal disorders | ||||||||||||||
| Ascites | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 1 |
| Colitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 2/11 (18.2%) | 2 | 0/11 (0%) | 0 | 3/56 (5.4%) | 6 |
| Diarrhea | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 5/11 (45.5%) | 9 | 3/11 (27.3%) | 3 | 11/56 (19.6%) | 14 |
| Enterocolitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 2 |
| Gastric hemorrhage | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Gastrointestinal disorders - Other, specify | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 5/56 (8.9%) | 5 |
| Gastrointestinal fistula | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Mucositis oral | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 2/11 (18.2%) | 3 | 9/56 (16.1%) | 11 |
| Oral pain | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Small intestinal perforation | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Typhlitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Vomiting | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| General disorders | ||||||||||||||
| Death NOS | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 3/56 (5.4%) | 3 |
| Fatigue | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Fever | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 2/11 (18.2%) | 2 | 3/56 (5.4%) | 4 |
| General disorders and administration site conditions - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Irritability | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Multi-organ failure | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Immune system disorders | ||||||||||||||
| Anaphylaxis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Immune system disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Infections and infestations | ||||||||||||||
| Abdominal infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Anorectal infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Bronchial infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Catheter related infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 2/11 (18.2%) | 3 | 2/11 (18.2%) | 3 | 6/56 (10.7%) | 6 |
| Endocarditis infective | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Enterocolitis infectious | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 3/56 (5.4%) | 3 |
| Hepatic infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Infections and infestations - Other, specify | 5/210 (2.4%) | 6 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 2/54 (3.7%) | 2 | 6/11 (54.5%) | 22 | 5/11 (45.5%) | 9 | 23/56 (41.1%) | 43 |
| Lung infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 2/54 (3.7%) | 3 | 3/11 (27.3%) | 4 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 1 |
| Mucosal infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Peritoneal infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Sepsis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 2/54 (3.7%) | 2 | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 1 | 11/56 (19.6%) | 14 |
| Skin infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 3/56 (5.4%) | 3 |
| Small intestine infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 2/56 (3.6%) | 2 |
| Soft tissue infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Tracheitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Upper respiratory infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Urinary tract infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 2/11 (18.2%) | 2 | 3/56 (5.4%) | 3 |
| Wound infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||
| Injury, poisoning and procedural complications - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Vascular access complication | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Investigations | ||||||||||||||
| Activated partial thromboplastin time prolonged | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Alanine aminotransferase increased | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 3/11 (27.3%) | 12 | 1/11 (9.1%) | 4 | 10/56 (17.9%) | 16 |
| Aspartate aminotransferase increased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 2 | 1/11 (9.1%) | 4 | 8/56 (14.3%) | 9 |
| Blood bilirubin increased | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 2/56 (3.6%) | 2 |
| Creatinine increased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Fibrinogen decreased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| GGT increased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Investigations - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Lipase increased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Lymphocyte count decreased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 2 | 1/56 (1.8%) | 2 |
| Neutrophil count decreased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 2 | 2/11 (18.2%) | 3 | 7/56 (12.5%) | 10 |
| Platelet count decreased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 2/11 (18.2%) | 3 | 3/56 (5.4%) | 6 |
| Weight loss | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 2/11 (18.2%) | 2 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| White blood cell decreased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 2 | 2/11 (18.2%) | 3 | 2/56 (3.6%) | 5 |
| Metabolism and nutrition disorders | ||||||||||||||
| Acidosis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Anorexia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 2/11 (18.2%) | 2 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 1 |
| Dehydration | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 2/11 (18.2%) | 3 | 2/11 (18.2%) | 2 | 6/56 (10.7%) | 9 |
| Hyperglycemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Hypernatremia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 2/11 (18.2%) | 2 | 1/56 (1.8%) | 1 |
| Hypertriglyceridemia | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hypoalbuminemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 5/56 (8.9%) | 6 |
| Hypocalcemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hypoglycemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 3/56 (5.4%) | 4 |
| Hypokalemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 2/11 (18.2%) | 3 | 1/11 (9.1%) | 1 | 6/56 (10.7%) | 6 |
| Hyponatremia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hypophosphatemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Treatment related secondary malignancy | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Nervous system disorders | ||||||||||||||
| Abducens nerve disorder | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Cognitive disturbance | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Depressed level of consciousness | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 2 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Encephalopathy | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 1 |
| Oculomotor nerve disorder | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Seizure | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 2/11 (18.2%) | 2 | 1/11 (9.1%) | 1 | 2/56 (3.6%) | 2 |
| Stroke | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Psychiatric disorders | ||||||||||||||
| Psychiatric disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Renal and urinary disorders | ||||||||||||||
| Acute kidney injury | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Adult respiratory distress syndrome | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Apnea | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Aspiration | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Atelectasis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Dyspnea | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hypoxia | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 1 | 2/11 (18.2%) | 2 | 4/56 (7.1%) | 4 |
| Pneumonitis | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 2 | 0/56 (0%) | 0 |
| Respiratory failure | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 4/56 (7.1%) | 5 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Rash maculo-papular | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 2/11 (18.2%) | 2 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, specify | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 3 |
| Skin ulceration | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 3/56 (5.4%) | 3 |
| Surgical and medical procedures | ||||||||||||||
| Surgical and medical procedures - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Vascular disorders | ||||||||||||||
| Hypertension | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hypotension | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 2/11 (18.2%) | 2 | 1/11 (9.1%) | 1 | 5/56 (8.9%) | 5 |
| Thromboembolic event | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Visceral arterial ischemia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Induction (All Patients) | Post Induction (Follow-up Only) | Arm A (Standard Risk MLL-G) | Arm B (IR/HR MLL-R Chemotherapy) | Arm C (Safety/ Dose Level 1) | Arm C (Safety/ Dose Level 2) | Arm C (Efficacy/ Dose Level 2) | ||||||||
| 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 | 181/210 (86.2%) | 5/12 (41.7%) | 59/60 (98.3%) | 54/54 (100%) | 11/11 (100%) | 11/11 (100%) | 55/56 (98.2%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anemia | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 4/60 (6.7%) | 7 | 4/54 (7.4%) | 7 | 1/11 (9.1%) | 2 | 1/11 (9.1%) | 1 | 5/56 (8.9%) | 7 |
| Blood and lymphatic system disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Disseminated intravascular coagulation | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Febrile neutropenia | 31/210 (14.8%) | 32 | 0/12 (0%) | 0 | 34/60 (56.7%) | 58 | 32/54 (59.3%) | 69 | 6/11 (54.5%) | 9 | 4/11 (36.4%) | 13 | 26/56 (46.4%) | 40 |
| Leukocytosis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Cardiac disorders | ||||||||||||||
| Cardiac arrest | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Cardiac disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Myocarditis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Sinus tachycardia | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 3/56 (5.4%) | 3 |
| Eye disorders | ||||||||||||||
| Blurred vision | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Eye disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||
| Abdominal distension | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Abdominal pain | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 2/11 (18.2%) | 2 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Anal mucositis | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 2/54 (3.7%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Anal pain | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Colitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 3/54 (5.6%) | 3 | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Diarrhea | 15/210 (7.1%) | 16 | 0/12 (0%) | 0 | 15/60 (25%) | 21 | 14/54 (25.9%) | 24 | 2/11 (18.2%) | 5 | 1/11 (9.1%) | 1 | 16/56 (28.6%) | 28 |
| Dysphagia | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 2/54 (3.7%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Enterocolitis | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Esophagitis | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Gastric hemorrhage | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Gastritis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Gastrointestinal disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 3/54 (5.6%) | 3 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Mucositis oral | 13/210 (6.2%) | 14 | 0/12 (0%) | 0 | 35/60 (58.3%) | 46 | 24/54 (44.4%) | 29 | 6/11 (54.5%) | 9 | 5/11 (45.5%) | 10 | 24/56 (42.9%) | 30 |
| Nausea | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 2/54 (3.7%) | 2 | 3/11 (27.3%) | 3 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Oral hemorrhage | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Oral pain | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 2/60 (3.3%) | 2 | 4/54 (7.4%) | 4 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Rectal mucositis | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 2/54 (3.7%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Small intestinal mucositis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Vomiting | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 2/60 (3.3%) | 3 | 6/54 (11.1%) | 6 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 4/56 (7.1%) | 4 |
| General disorders | ||||||||||||||
| Death NOS | 0/210 (0%) | 0 | 3/12 (25%) | 3 | 0/60 (0%) | 0 | 10/54 (18.5%) | 10 | 3/11 (27.3%) | 3 | 1/11 (9.1%) | 1 | 3/56 (5.4%) | 3 |
| Edema face | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Fatigue | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Fever | 2/210 (1%) | 3 | 0/12 (0%) | 0 | 9/60 (15%) | 12 | 6/54 (11.1%) | 7 | 2/11 (18.2%) | 2 | 2/11 (18.2%) | 3 | 2/56 (3.6%) | 2 |
| General disorders and administration site conditions - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 2/54 (3.7%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Hypothermia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Infusion related reaction | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Irritability | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 2/54 (3.7%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 2 |
| Multi-organ failure | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pain | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 2/60 (3.3%) | 2 | 2/54 (3.7%) | 3 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 3/56 (5.4%) | 3 |
| Hepatobiliary disorders | ||||||||||||||
| Hepatic failure | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Immune system disorders | ||||||||||||||
| Allergic reaction | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Anaphylaxis | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 2/60 (3.3%) | 2 | 2/54 (3.7%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Immune system disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 2/54 (3.7%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Infections and infestations | ||||||||||||||
| Anorectal infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 3/54 (5.6%) | 3 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Bladder infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 2 |
| Bronchial infection | 2/210 (1%) | 3 | 0/12 (0%) | 0 | 3/60 (5%) | 3 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Catheter related infection | 5/210 (2.4%) | 6 | 0/12 (0%) | 0 | 13/60 (21.7%) | 20 | 12/54 (22.2%) | 21 | 3/11 (27.3%) | 4 | 1/11 (9.1%) | 3 | 8/56 (14.3%) | 10 |
| Endocarditis infective | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 3 |
| Enterocolitis infectious | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 3/60 (5%) | 3 | 7/54 (13%) | 8 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Infections and infestations - Other, specify | 52/210 (24.8%) | 66 | 0/12 (0%) | 0 | 32/60 (53.3%) | 66 | 36/54 (66.7%) | 116 | 4/11 (36.4%) | 18 | 8/11 (72.7%) | 11 | 19/56 (33.9%) | 39 |
| Lung infection | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 5/60 (8.3%) | 5 | 7/54 (13%) | 11 | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 1 | 5/56 (8.9%) | 6 |
| Meningitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Mucosal infection | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Otitis media | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 3/54 (5.6%) | 3 | 0/11 (0%) | 0 | 1/11 (9.1%) | 2 | 4/56 (7.1%) | 5 |
| Paronychia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Penile infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 2/60 (3.3%) | 2 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pharyngitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Rash pustular | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 2 | 0/56 (0%) | 0 |
| Scrotal infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 2 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Sepsis | 7/210 (3.3%) | 7 | 0/12 (0%) | 0 | 2/60 (3.3%) | 2 | 10/54 (18.5%) | 15 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 5/56 (8.9%) | 7 |
| Sinusitis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 3/54 (5.6%) | 3 | 2/11 (18.2%) | 2 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Skin infection | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 7/60 (11.7%) | 8 | 7/54 (13%) | 9 | 2/11 (18.2%) | 2 | 3/11 (27.3%) | 4 | 1/56 (1.8%) | 2 |
| Small intestine infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Soft tissue infection | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 3/60 (5%) | 4 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Upper respiratory infection | 6/210 (2.9%) | 6 | 0/12 (0%) | 0 | 7/60 (11.7%) | 9 | 10/54 (18.5%) | 15 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 6/56 (10.7%) | 6 |
| Urinary tract infection | 6/210 (2.9%) | 6 | 0/12 (0%) | 0 | 7/60 (11.7%) | 9 | 21/54 (38.9%) | 30 | 1/11 (9.1%) | 2 | 3/11 (27.3%) | 4 | 13/56 (23.2%) | 14 |
| Vulval infection | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Wound infection | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||||
| Fracture | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Intraoperative hemorrhage | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Vascular access complication | 5/210 (2.4%) | 5 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Wound complication | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Investigations | ||||||||||||||
| Activated partial thromboplastin time prolonged | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Alanine aminotransferase increased | 24/210 (11.4%) | 24 | 0/12 (0%) | 0 | 42/60 (70%) | 94 | 35/54 (64.8%) | 84 | 8/11 (72.7%) | 32 | 7/11 (63.6%) | 12 | 30/56 (53.6%) | 57 |
| Alkaline phosphatase increased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 4/60 (6.7%) | 4 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 2 |
| Aspartate aminotransferase increased | 15/210 (7.1%) | 15 | 0/12 (0%) | 0 | 34/60 (56.7%) | 52 | 28/54 (51.9%) | 59 | 5/11 (45.5%) | 11 | 4/11 (36.4%) | 5 | 21/56 (37.5%) | 31 |
| Blood bilirubin increased | 2/210 (1%) | 3 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 4/54 (7.4%) | 4 | 2/11 (18.2%) | 3 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Creatinine increased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| GGT increased | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 3/60 (5%) | 7 | 3/54 (5.6%) | 4 | 2/11 (18.2%) | 7 | 0/11 (0%) | 0 | 3/56 (5.4%) | 7 |
| Investigations - Other, specify | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 4 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Lipase increased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Lymphocyte count decreased | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 3/60 (5%) | 3 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Neutrophil count decreased | 74/210 (35.2%) | 76 | 0/12 (0%) | 0 | 29/60 (48.3%) | 62 | 26/54 (48.1%) | 45 | 9/11 (81.8%) | 15 | 5/11 (45.5%) | 8 | 26/56 (46.4%) | 48 |
| Platelet count decreased | 9/210 (4.3%) | 9 | 0/12 (0%) | 0 | 9/60 (15%) | 13 | 16/54 (29.6%) | 24 | 4/11 (36.4%) | 8 | 3/11 (27.3%) | 5 | 12/56 (21.4%) | 18 |
| Urine output decreased | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 2 |
| Weight gain | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Weight loss | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 4/60 (6.7%) | 9 | 7/54 (13%) | 12 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| White blood cell decreased | 6/210 (2.9%) | 6 | 0/12 (0%) | 0 | 14/60 (23.3%) | 19 | 9/54 (16.7%) | 13 | 2/11 (18.2%) | 5 | 1/11 (9.1%) | 1 | 8/56 (14.3%) | 16 |
| Metabolism and nutrition disorders | ||||||||||||||
| Acidosis | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 2/54 (3.7%) | 3 | 1/11 (9.1%) | 2 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Anorexia | 18/210 (8.6%) | 18 | 0/12 (0%) | 0 | 13/60 (21.7%) | 28 | 15/54 (27.8%) | 31 | 2/11 (18.2%) | 2 | 2/11 (18.2%) | 5 | 9/56 (16.1%) | 29 |
| Dehydration | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 8/60 (13.3%) | 10 | 9/54 (16.7%) | 16 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 5/56 (8.9%) | 5 |
| Hypercalcemia | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hyperglycemia | 19/210 (9%) | 19 | 0/12 (0%) | 0 | 4/60 (6.7%) | 5 | 9/54 (16.7%) | 17 | 3/11 (27.3%) | 3 | 2/11 (18.2%) | 2 | 7/56 (12.5%) | 8 |
| Hyperkalemia | 6/210 (2.9%) | 6 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 3/54 (5.6%) | 4 | 2/11 (18.2%) | 2 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Hypernatremia | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Hypertriglyceridemia | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 2/54 (3.7%) | 2 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Hypoalbuminemia | 15/210 (7.1%) | 15 | 0/12 (0%) | 0 | 3/60 (5%) | 3 | 5/54 (9.3%) | 6 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 5/56 (8.9%) | 6 |
| Hypocalcemia | 29/210 (13.8%) | 29 | 0/12 (0%) | 0 | 5/60 (8.3%) | 6 | 3/54 (5.6%) | 5 | 0/11 (0%) | 0 | 3/11 (27.3%) | 3 | 5/56 (8.9%) | 6 |
| Hypoglycemia | 5/210 (2.4%) | 5 | 0/12 (0%) | 0 | 4/60 (6.7%) | 6 | 2/54 (3.7%) | 2 | 3/11 (27.3%) | 5 | 0/11 (0%) | 0 | 7/56 (12.5%) | 8 |
| Hypokalemia | 35/210 (16.7%) | 36 | 0/12 (0%) | 0 | 20/60 (33.3%) | 37 | 14/54 (25.9%) | 41 | 6/11 (54.5%) | 16 | 3/11 (27.3%) | 4 | 22/56 (39.3%) | 37 |
| Hypomagnesemia | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 3 |
| Hyponatremia | 14/210 (6.7%) | 14 | 0/12 (0%) | 0 | 5/60 (8.3%) | 8 | 8/54 (14.8%) | 9 | 2/11 (18.2%) | 3 | 1/11 (9.1%) | 1 | 2/56 (3.6%) | 3 |
| Hypophosphatemia | 5/210 (2.4%) | 5 | 0/12 (0%) | 0 | 2/60 (3.3%) | 3 | 2/54 (3.7%) | 2 | 3/11 (27.3%) | 4 | 0/11 (0%) | 0 | 3/56 (5.4%) | 3 |
| Metabolism and nutrition disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Generalized muscle weakness | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Muscle weakness trunk | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pain in extremity | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 0/56 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Leukemia secondary to oncology chemotherapy | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 2/56 (3.6%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 4/54 (7.4%) | 4 | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 1 | 1/56 (1.8%) | 1 |
| Nervous system disorders | ||||||||||||||
| Encephalopathy | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Intracranial hemorrhage | 0/210 (0%) | 0 | 1/12 (8.3%) | 1 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Nervous system disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Peripheral motor neuropathy | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 3 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Peripheral sensory neuropathy | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 3 |
| Psychiatric disorders | ||||||||||||||
| Insomnia | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||
| Acute kidney injury | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hematuria | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Renal and urinary disorders - Other, specify | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Reproductive system and breast disorders | ||||||||||||||
| Penile pain | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Adult respiratory distress syndrome | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Atelectasis | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Bronchopulmonary hemorrhage | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Cough | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Dyspnea | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Epistaxis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 2 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Hypoxia | 6/210 (2.9%) | 6 | 0/12 (0%) | 0 | 4/60 (6.7%) | 8 | 3/54 (5.6%) | 5 | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 | 4/56 (7.1%) | 4 |
| Laryngeal mucositis | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Pharyngeal mucositis | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pleural effusion | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pneumonitis | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 1/54 (1.9%) | 2 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pneumothorax | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pulmonary edema | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Respiratory failure | 1/210 (0.5%) | 1 | 1/12 (8.3%) | 1 | 1/60 (1.7%) | 1 | 3/54 (5.6%) | 3 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 4/54 (7.4%) | 7 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Sinus disorder | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Stridor | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 2 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Dry skin | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Erythema multiforme | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 2/60 (3.3%) | 2 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Pain of skin | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 2/60 (3.3%) | 2 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Periorbital edema | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Pruritus | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Rash maculo-papular | 3/210 (1.4%) | 3 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Skin and subcutaneous tissue disorders - Other, specify | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 3/60 (5%) | 4 | 4/54 (7.4%) | 6 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Skin induration | 0/210 (0%) | 0 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Skin ulceration | 12/210 (5.7%) | 12 | 0/12 (0%) | 0 | 5/60 (8.3%) | 5 | 3/54 (5.6%) | 3 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 8/56 (14.3%) | 10 |
| Surgical and medical procedures | ||||||||||||||
| Surgical and medical procedures - Other, specify | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 0/54 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
| Vascular disorders | ||||||||||||||
| Hypertension | 25/210 (11.9%) | 25 | 0/12 (0%) | 0 | 1/60 (1.7%) | 1 | 5/54 (9.3%) | 8 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hypotension | 4/210 (1.9%) | 4 | 0/12 (0%) | 0 | 1/60 (1.7%) | 2 | 5/54 (9.3%) | 5 | 2/11 (18.2%) | 3 | 1/11 (9.1%) | 1 | 4/56 (7.1%) | 4 |
| Thromboembolic event | 2/210 (1%) | 2 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 3/54 (5.6%) | 3 | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 | 1/56 (1.8%) | 1 |
| Vascular disorders - Other, specify | 1/210 (0.5%) | 1 | 0/12 (0%) | 0 | 0/60 (0%) | 0 | 1/54 (1.9%) | 1 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/56 (0%) | 0 |
Limitations/Caveats
Data was and never will be collected for Outcome Measure #4, 5, 12, and 13.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Must obtain sponsor approval.
Results Point of Contact
| Name/Title | Results Reporting Coordinator |
|---|---|
| Organization | Children's Oncology Group |
| Phone | 626-447-0064 |
| resultsreportingcoordinator@childrensoncologygroup.org |
Responsible Party:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00557193
Other Study ID Numbers:
- AALL0631
- NCI-2009-00313
- COG-AALL0631
- 08-146
- CDR0000573996
- AALL0631
- AALL0631
- U10CA180886
- U10CA098543
First Posted:
Nov 12, 2007
Last Update Posted:
Mar 25, 2022
Last Verified:
Mar 1, 2022