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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00557193
First received: November 9, 2007
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This phase III trial is studying giving lestaurtinib together with combination chemotherapy to see how well it works compared to combination chemotherapy alone in treating infants 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 or by stopping them from dividing. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) together with lestaurtinib may kill more cancer cells.


Condition Intervention Phase
Acute Undifferentiated Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Drug: asparaginase
Drug: daunorubicin hydrochloride
Drug: lestaurtinib
Drug: cyclophosphamide
Drug: pegaspargase
Drug: prednisone
Drug: methylprednisolone
Drug: dexamethasone
Drug: cytarabine
Drug: methotrexate
Biological: filgrastim
Drug: leucovorin calcium
Drug: etoposide
Drug: mercaptopurine
Drug: vincristine sulfate
Drug: hydrocortisone sodium succinate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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; IND #76431; NSC#617807)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival of MLL-R infants randomized to a modified P9407 backbone with or without lestaurtinib [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
    All randomized patients will be included in the intent-to-treat efficacy analyses. Event-free survival time will be calculated from the time of randomization, which is just prior to beginning Induction Intensification.


Secondary Outcome Measures:
  • Safe, tolerable, and biologically active dose of lestaurtinib as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Lestaurtinib-related dose limiting toxicity (DLT) is defined as any grade 4 non-hematologic (i.e., excluding blood/bone marrow) toxicity that occurs after the first dose of lestaurtinib and is at least possibly related to lestaurtinib. Any grade 3 non-hematologic (i.e., excluding blood/bone marrow) toxicity that occurs after the first dose of lestaurtinib, is at least possibly attributable to lestaurtinib and results in omission or delay of the beginning of the subsequent course of chemotherapy for greater than 7 days.

  • Pharmacokinetic profile of lestaurtinib by plasma inhibitory activity (PIA) assay [ Time Frame: At baseline and during weeks 6-9 and 10-12 of lestaurinib treatment ] [ Designated as safety issue: No ]
    Cells (FLT3/ITD) incubated with plasma are washed, lysed, and analyzed for FLT3 phosphorylation by FLT3 immunoprecipitation and sequential immunoblotting with 4G10 anti-phosphotyrosine antibody and anti-FLT3 antibody. Densitometric analysis will be used to calculate the PIA (the percent inhibition of FLT3 phosphorylation of each timepoint relative to the pre-treatment sample). These results will be used to determine whether a given dose of lestaurtinib is biologically active.


Estimated Enrollment: 315
Study Start Date: January 2008
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Post-induction chemotherapy A)
Patients receive induction therapy (weeks 1-5) comprising vincristine sulfate (VCR) IV; daunorubicin hydrochloride (DNR) IV; cyclophosphamide (CPM) IV; pegaspargase (PEG) or asparaginase (ASP) IM; prednisone (PED) PO or methylprednisolone IV; dexamethasone (DEX) IV or PO; cytarabine (ARAC) IV; methotrexate (MTX), ARAC, and hydrocortisone sodium succinate (HC) IT [triple IT chemotherapy]; and filgrastim IV or SC. Patients then receive post-induction therapy A comprising high-dose (HD) MTX; triple IT chemotherapy; leucovorin calcium IV; CPM; etoposide IV, VCR; DNR; PEG and ASP; DEX; HD ARAC; mercaptopurine PO; and filgrastim IV or SC for up to 104 weeks.
Drug: asparaginase
Given IV, IM, or PO
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: cytarabine
Given IV or IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: methotrexate
Given IV, IT, or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Active Comparator: Treatment (Post-induction chemotherapy B)
Patients receive induction therapy (weeks 1-5) comprising vincristine sulfate (VCR) IV; daunorubicin hydrochloride (DNR) IV; cyclophosphamide (CPM) IV; pegaspargase (PEG) or asparaginase (ASP) IM; prednisone (PED) PO or methylprednisolone IV; dexamethasone (DEX) IV or PO; cytarabine (ARAC) IV; methotrexate (MTX), ARAC, and hydrocortisone sodium succinate (HC) IT [triple IT chemotherapy]; and filgrastim IV or SC. Patients then receive post-induction therapy B comprising high-dose (HD) MTX; triple IT chemotherapy; leucovorin calcium IV; CPM; etoposide IV, VCR; DNR; PEG and ASP; DEX; HD ARAC; mercaptopurine PO; and filgrastim IV or SC for up to 104 weeks.
Drug: asparaginase
Given IV, IM, or PO
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: cytarabine
Given IV or IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: methotrexate
Given IV, IT, or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: Treatment (Post-induction chemotherapy C)
Patients receive induction therapy (weeks 1-5) comprising vincristine sulfate (VCR) IV; daunorubicin hydrochloride (DNR) IV; cyclophosphamide (CPM) IV; pegaspargase (PEG) or asparaginase (ASP) IM; prednisone (PED) PO or methylprednisolone IV; dexamethasone (DEX) IV or PO; cytarabine (ARAC) IV; methotrexate (MTX), ARAC, and hydrocortisone sodium succinate (HC) IT [triple IT chemotherapy]; and filgrastim IV or SC. Patients then receive post-induction therapy C comprising high-dose (HD) MTX; lestaurtinib PO; triple IT chemotherapy; leucovorin calcium IV; CPM; etoposide IV, VCR; DNR; PEG and ASP; DEX; HD ARAC; mercaptopurine PO; and filgrastim IV or SC for up to 104 weeks.
Drug: asparaginase
Given IV, IM, or PO
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: lestaurtinib
Given PO
Other Names:
  • CEP 701
  • CEP-701
  • KT-5555
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: cytarabine
Given IV or IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: methotrexate
Given IV, IT, or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 1 Year
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be enrolled on a 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 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 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, FDA, and NCI requirements for human studies must be met
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557193

  Show 159 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Joanne Hilden, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00557193     History of Changes
Other Study ID Numbers: AALL0631, NCI-2009-00313, COG-AALL0631, CDR0000573996, U10CA098543
Study First Received: November 9, 2007
Last Updated: June 30, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
6-Mercaptopurine
Cytarabine
Methotrexate
Cyclophosphamide
Etoposide phosphate
Pegaspargase
Asparaginase
Daunorubicin
Dexamethasone
Etoposide
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Vincristine
BB 1101
Lenograstim
Dexamethasone acetate
Cortisol succinate
Hydrocortisone acetate

ClinicalTrials.gov processed this record on July 20, 2014