Phase III Randomized Trial of Autologous and Allogeneic Stem Cell Transplantation Versus Intensive Conventional Chemotherapy in Acute Lymphoblastic Leukemia in First Remission

OBJECTIVES:

• Compare the duration of complete remission (CR) and survival in patients with acute lymphoblastic leukemia in first remission treated with allogeneic or autologous stem cell transplantation (SCT) vs conventional consolidation and maintenance chemotherapy.
• Compare the overall treatment outcomes in patients treated with these regimens.
• Determine the effect of imatinib mesylate given after induction therapy in Philadelphia (Ph) chromosome-positive patients in CR.
• Determine the benefit of allogeneic or autologous SCT after imatinib mesylate in Ph chromosome-positive patients.
• Determine the benefit of additional imatinib mesylate administered after allogeneic or autologous SCT in Ph chromosome-positive patients.
• Determine the minimal residual disease in Ph chromosome-positive patients before and after treatment with imatinib mesylate.
• Determine the clinical resistance to imatinib mesylate caused by BCR-ABL gene amplification or mutation in Ph chromosome-positive patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (50 and under vs over 50), time to achieve complete remission (CR) (4 weeks or less vs more than 4 weeks), and Philadelphia (Ph) chromosome status (positive vs negative).

• First induction therapy: Patients receive daunorubicin (DNR) IV over 15-30 minutes and vincristine (VCR) IV over 3-5 minutes on days 1, 8, 15, and 22; oral prednisone (PRED) once daily on days 1-28; and asparaginase (ASP) IV over 30 minutes or intramuscularly on days 17-28. Patients with CNS leukemia at presentation also receive methotrexate (MTX) intrathecally (IT) via an Ommaya reservoir weekly until the CSF is clear. Patients without CNS leukemia at presentation receive MTX IT on day 23 only.
• Second induction therapy: Beginning immediately after first induction therapy, patients receive cyclophosphamide (CTX) IV over 30 minutes on days 1, 15, and 29; cytarabine (ARA-C) IV over 30 minutes on days 1-4, 8-11, 15-18, and 22-25; and oral mercaptopurine (MP) once daily on days 1-28. Patients with CNS leukemia at presentation also undergo concurrent craniospinal irradiation. Patients without CNS leukemia at presentation receive MTX IT on days 1, 8, 15, and 22. Patients with Ph chromosome-positive status receive oral imatinib mesylate once daily for at least 28 days (days 1-28).

Patients with Ph chromosome-positive status and CR after second induction therapy proceed to group I for autologous or allogeneic stem cell transplantation (SCT). Patients with Ph chromosome-negative status and CR after second induction therapy proceed to group II.