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RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methotrexate, leucovorin, and antithymocyte globulin before and after transplant may stop this from happening. It is not yet known which treatment regimen is most effective in treating acute leukemia.
PURPOSE: This randomized clinical trial is studying how well different therapies work in treating infants with newly diagnosed acute leukemia.
Full description
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Induction therapy:
NOTE: *Patients with CNS involvement at initial diagnosis also receive MTX IT on days 8 and 22. If CNS leukemia is still present at day 29, then patients receive weekly MTX IT until the CNS is free of leukemia.
After completion of induction therapy, patients are stratified according to risk group (low-risk [LR] vs medium-risk [MR] vs high-risk [HR]). Patients with low-risk disease are assigned to treatment arm I. Patients with MR or HR disease that is in complete remission (CR) on day 33 are randomized to 1 of 2 treatment arms. These patients are stratified according to status (MR with rearranged MLL vs MR with unknown MLL vs HR).
Arm I (standard therapy):
Protocol IB therapy (beginning on day 36 of induction therapy): Patients receive cyclophosphamide (CPM) IV over 1 hour on days 1 and 29 and oral mercaptopurine (MP) on days 1-28; ARA-C IV on days 3-6, 10-13, 17-20, and 24-27; ARA-C IT on day 10; and MTX IT on day 24. Patients also receive PRDL or therapeutic HC IT on days 10 and 24.
MARMA therapy:
OCTADA(D) reinduction therapy:
Maintenance therapy: At least 2 weeks after completion of the last course of OCTADA(D) chemotherapy, patients receive oral MP once daily; oral MTX once weekly; MTX IT in weeks 1 and 15; and ARA-C IT in week 8. Patients also receive PRDL or therapeutic HC IT in weeks 1, 8, and 15. Treatment continues for up to 104 weeks after initial diagnosis in the absence of disease progression or unacceptable toxicity.
Arm II (experimental therapy):
ADE therapy (beginning on day 36 of induction therapy: Patients receive ARA-C IV every 12 hours on days 1-10; DNR IV over 1 hour on days 1, 3, and 5; etoposide (VP-16) IV over 4 hours on days 1-5; and ARA-C IT on day 1. Patients also receive PRDL or therapeutic HC IT on day 1.
MAE therapy: Patients receive ARA-C IV every 12 hours on days 1-10; mitoxantrone hydrochloride IV over 1 hour on days 1, 3, and 5; VP-16 IV over 4 hours on days 1-5; and MTX IT on day 1. Patients also receive PRDL or therapeutic HC IT on day 1.
MARMA therapy:
OCTADA reinduction therapy:
Maintenance therapy: At least 2 weeks after completion of the last course of OCTADA chemotherapy, patients receive oral MP once daily; oral MTX once weekly; MTX IT in weeks 1 and 15; and ARA-C IT in week 8. Patients also receive PRDL or therapeutic HC IT in weeks 1, 8, and 15. Treatment continues for up to 104 weeks after initial diagnosis in the absence of disease progression or unacceptable toxicity.
All HR patients with a suitably matched donor are scheduled for allogeneic stem cell transplantation (SCT) after MARMA or before or during OCTADA(D) chemotherapy, provided they are in CR1 and no more than 8 months have elapsed since initial diagnosis.
Conditioning regimens for allogeneic SCT:
Graft-Versus-Host Disease (GVHD) prophylaxis and therapy:
Allogeneic SCT: Patients undergo infusion of bone marrow, peripheral blood, or cord blood hematopoietic stem cells on day 0.
After completion of study therapy, patients are followed periodically for up to 2 years.
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Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
Inclusion criteria:
Diagnosis of acute lymphoblastic leukemia (ALL) or biphenotypic leukemia meeting the following criteria:
Based on European Group for the Classification of Acute Leukemia (EGIL) diagnostic criteria
Newly diagnosed disease
Verified by morphology and confirmed by cytochemistry and immunophenotyping
Must have MLL gene rearrangements documented by split-signal fluorescence in situ hybridization and meets 1 of the following risk criteria:
Low-risk disease, defined as all MLL germline cases
Medium-risk disease, defined by 1 of the following criteria:
High-risk disease, defined by MLL rearrangement AND meets the following criteria:
Minimum donor and stem cell requirements for high-risk patients undergoing stem cell transplantation:
Donor meeting 1 of the following criteria:
Stem cell source
Bone marrow (preferred source) OR peripheral blood stem cells of filgrastim [G-CSF]-stimulated donors OR cord blood
Must have ≥ 3 x 10^8 NCs/kg BW OR 3 x 10^6/kg BW CD34-positive cells available for transplantation
CNS or testicular leukemia at diagnosis allowed
Exclusion criteria:
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
More than 4 weeks since prior systemic corticosteroids
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Data sourced from clinicaltrials.gov
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