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Methotrexate

Patients complete neurocognitive tests to assess thinking, memory, attention, and concentration. The baseline test is administered during the consolidation phase of chemotherapy and further tests are done at 1 year from baseline and 1 year after\* the completion of study therapy.

Patients undergo blood and cerebrospinal fluid collection periodically for biomarker, genotypic polymorphisms, and pharmacokinetic analysis. Patients undergo MRI diffusion-tensor imaging to correlate imaging with neuropsychological outcomes.

Cognitive Assessment

Diffusion Tensor Imaging

Laboratory Biomarker Analysis

Pharmacological Study

Psychosocial Assessment and Care

Naomi Winick

This clinical trial is looking at brain function in young patients receiving methotrexate for acute lymphoblastic leukemia. Learning about the long-term effects of methotrexate on brain function may help doctors plan cancer treatment.

OBJECTIVES:

I. Determine the neuropsychological function in children with acute lymphoblastic leukemia treated with either high-dose methotrexate or escalating-dose methotrexate in the absence of cranial radiation and nelarabine.

II. Identify host polymorphisms that predict an increased risk of neurocognitive dysfunction or acute neurotoxicity in these patients.

III. Correlate neuropsychological outcome measures and the occurrence of acute neurotoxicity with host polymorphisms in these patients.

IV. Measure concentrations of 5-methyltetrahydrofolate, homocysteine, Ado, S-adenosylmethionine, S-adenosylhomocysteine, and other potentially relevant compounds in serum and cerebrospinal fluid during interim maintenance therapy with low- or high-dose methotrexate regimens, respectively, and correlate these endpoints with the occurrence of acute neurologic toxicity and long-term neurocognitive dysfunction in these patients.

V. Determine whether or not diffusion tensor imaging will identify areas of selective vulnerability in CNS and provide an imaging modality that predicts and/or correlates with neuropsychological outcome.

OUTLINE: This is a prospective, cohort, multicenter study.

Patients complete neurocognitive tests to assess thinking, memory, attention, and concentration. The baseline test is administered during the consolidation phase of chemotherapy and further tests are done at 1 year from baseline and 1 year after\* the completion of study therapy.

Patients undergo blood and cerebrospinal fluid collection periodically for biomarker, genotypic polymorphisms, and pharmacokinetic analysis. Patients undergo MRI diffusion-tensor imaging to correlate imaging with neuropsychological outcomes.

NOTE: \* Within 8 months to 24 months after the completion of study therapy for patients on AALL0232.

Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

A Study of Neurocognitive Function in Children Treated for ALL

Vocabulary and Block Design, subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Wechsler Children Intelligence Scale (WISC-IV) and Wechsler Adult Intelligence Scale (WAIS-III) (based on age) will be used to estimate FSIQ, using the tables provided by Sattler.

National Cancer Institute (NCI)

Children's Oncology Group

Micronutrients

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Hematinics

Neuroprotective Agents

Bone Density Conservation Agents

Vitamins

Amino Acids

Leucovorin

Dexamethasone

Etoposide

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Cytarabine

Cyclophosphamide

Levoleucovorin

Prednisone

Vincristine

Daunorubicin

Prednisolone

Calcium

Lenograstim

Dexamethasone acetate

BB 1101

Pegaspargase

Folic Acid

Etoposide phosphate

Podophyllotoxin

Mercaptopurine

Methylprednisolone

Cortisone

Calcium, Dietary

Asparaginase

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Ichthammol

N-Methylaspartate

Vitamin B Complex

Hydrocortisone-17-butyrate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

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Adjuvants, Immunologic

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Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Keratolytic Agents

Folinic Acid

Folate

Vitamin B9

Aspartic Acid

Asparagine

Population Description: Eligible patients with MLL-G (germline, or non-rearranged)

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.

Biospecimen Collection

Bone Marrow Biopsy

Daunorubicin Hydrochloride

Echocardiography

Filgrastim

Lestaurtinib

Leucovorin Calcium

Multigated Acquisition Scan

Therapeutic Hydrocortisone

Vincristine Sulfate

Joanne M Hilden

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.

PRIMARY OBJECTIVES:

I. 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:

I. 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.

II. To determine a safe, tolerable and biologically active dose of lestaurtinib given in sequential combination with chemotherapy in MLL-R infants.

III. To characterize the pharmacokinetics and pharmacodynamics of lestaurtinib in infants when given at the proposed dose in sequential combination with chemotherapy.

IV. To identify molecular mechanisms of resistance to lestaurtinib in leukemic blasts.

V. To describe levels of minimal residual disease in infants with ALL within the context of the proposed therapy, and correlate with outcome.

VI. To identify gene expression patterns in diagnostic infant leukemia samples that correlate with outcome within the context of the proposed therapy.

VII. 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). Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), blood sample collection and bone marrow biopsy on day 1 week 1.

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. Patients may undergo bone marrow biopsy on day 1 week 6.

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. Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 10.

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. Patients may undergo bone marrow biopsy on day 1 week 20.

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 Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 6. (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. Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 10. (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. Patients may undergo bone marrow biopsy on day 1 of weeks 20, 33 and 46. (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.Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 6.

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. Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 10.

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. Patients may undergo bone marrow biopsy on day 1 of weeks 20, 33 and 46.

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.

Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

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)

Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

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.

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.

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 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 will be described with mean and standard deviation for those with available data.

Summarized with mean and standard deviation for those with available data in Arm C

Described via mean and standard deviation by group.

Described via means and standard deviations in available Arm C relapse samples

Described via means and standard deviations in samples which have primary resistance to lestaurtinib

Described via means and standard deviations in samples which have acquired resistance to lestaurtinib

Three-year EFS estimates and 90% CI will be reported by treatment arm and end-induction MRD status.

EFS outcomes will be reported by genotype.

Means and standard deviations of Plasma Inhibitory Activity (PIA) will be given by genotype

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.

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.

All Patients for Induction (not assigned)

Induction (All Patients)

Post-Induction patients that did not receive therapy

Post Induction (Follow-up Only)

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

Arm A (Standard Risk MLL-G)

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 B (IR/HR MLL-R Chemotherapy)

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 (Safety/ Dose Level 1)

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 (Safety/ Dose Level 2)

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)

Arm C (Efficacy/ Dose Level 2)

All Patients

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Canada

New Zealand

Australia

Region of Enrollment

Data was and never will be collected for Outcome Measure #4, 5, 12, and 13.

Results Reporting Coordinator

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)

Arm C (Safety/Efficacy Dose Level 2)

All 67 patients on Arm C (Safety and Efficacy at Dose Level 2) were included in the analysis.

Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2)

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.

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

Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)

All eligible Arm B and ARM C (Dose Level 2) patients were included in the analysis.

Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2

Evaluable Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at DL1 (HR: 3.5 mg/kg/day; SR: 4 mg/kg/day)

Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 1)

Evaluable Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day)

Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 2)

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.

Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT)

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia	NCT00437060	Childhood B Acu... Childhood T Acu... Cognitive Side ... Long-Term Effec... Neurotoxicity S... Psychological I... Untreated Child...	Cognitive Asses... Diffusion Tenso... Laboratory Biom... Pharmacological... Psychosocial As...	1 Year - 17 Years	Children's Oncology Group
Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia	NCT00557193	Acute Lymphobla... Acute Undiffere... Childhood T Acu...	Asparaginase Biospecimen Col... Bone Marrow Bio... Cyclophosphamid... Cytarabine Daunorubicin Hy... Dexamethasone Echocardiograph... Etoposide Filgrastim Laboratory Biom... Lestaurtinib Leucovorin Calc... Mercaptopurine Methotrexate Methylprednisol... Multigated Acqu... Pegaspargase Pharmacological... Prednisone Therapeutic Hyd... Vincristine Sul...	- 1 Year	Children's Oncology Group
Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma	NCT01403415	Childhood B Acu... Childhood T Acu... Mature T-Cell a... Recurrent Child... Recurrent Child...	Dexamethasone Laboratory Biom... Methotrexate Mitoxantrone Hy... Pegaspargase Pharmacological... Temsirolimus Vincristine Sul...	1 Year - 21 Years	National Cancer Institute (NCI)
Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia	NCT00557193	Acute Lymphobla... Acute Undiffere... Childhood T Acu...	Asparaginase Biospecimen Col... Bone Marrow Bio... Cyclophosphamid... Cytarabine Daunorubicin Hy... Dexamethasone Echocardiograph... Etoposide Filgrastim Laboratory Biom... Lestaurtinib Leucovorin Calc... Mercaptopurine Methotrexate Methylprednisol... Multigated Acqu... Pegaspargase Pharmacological... Prednisone Therapeutic Hyd... Vincristine Sul...	- 1 Year	Children's Oncology Group

Spots Global Cancer Trial Database for childhood t acute lymphoblastic leukemia