Trial Information

Randomized Multicenter Treatment Optimization Study In Chronic Myeloid Leukemia (CML) Interferon-a Vs. Allogeneic Stem Cell Transplantation Vs. High-Dose Chemotherapy Followed By Autografting And Interferon-a Maintainance In Early Chronic Phase

OBJECTIVES:

- Compare survival in patients with chronic myelogenous leukemia in early chronic phase
treated with allogeneic bone marrow transplantation vs drug treatment with or without
autologous peripheral blood stem cell transplantation.

- Compare survival of patients with late-phase disease treated with high-dose cytarabine
vs low-dose cytarabine followed by autografting and interferon alfa maintenance.

- Compare survival of patients not responding cytogenetically to treatment with continued
interferon alfa vs hydroxyurea.

- Determine frequency, time-point, and duration of hematological and cytogenetic
remissions and of Philadelphia chromosome-negative and/or BCR-ABL-positive cells on the
various treatments.

- Correlate the quality of hematological and cytogenetic remissions with survival time in
patients treated with these regimens.

- Compare the course of the terminal phase in patients treated with these regimens.

- Compare the toxic effects of these regimens in these patients.

- Determine the effect of prognostic criteria and normal or subnormal WBC on chronic
phase duration and survival time in patients treated with these regimens.

- Compare the effect of early vs late high-dose therapy plus autografting on feasibility,
toxicity, and survival times in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
eligibility for transplantation (yes vs no).

All patients undergo cytoreduction comprising hydroxyurea (HU) IV daily.

Patients who are ineligible for or refuse transplantation are randomized to 1 of 2 treatment
arms.

- Arm I: Patients receive interferon alfa (IFN) subcutaneously (SC) daily. After 2 weeks
of IFN therapy, patients also receive low-dose cytarabine (ARA-C) SC once daily for
10-15 days each month. Patients who do not achieve cytogenetic remission within 12
months continue to receive HU.

- Arm II: Patients receive IFN SC daily. After 2 weeks of IFN therapy, patients also
receive low-dose ARA-C SC daily for 10-15 days each month. Patients who do not achieve
cytogenetic remission within 12 months continue to receive IFN therapy SC daily.

Patients who are eligible for transplantation with a related donor undergo allogeneic bone
marrow transplantation. Patients may receive HU or IFN prior to transplantation. Patients
may also receive oral high-dose busulfan daily for 4 days with or without cyclophosphamide
or cyclophosphamide with total body irradiation.

Patients who are eligible for transplantation but do not have a related donor undergo
peripheral blood stem cell (PBSC) harvest and are randomized to 1 of 2 treatment arms.

- Arm III: Patients receive IFN and low-dose ARA-C as in arm I. Patients who accelerate
on treatment may undergo autologous PBSC transplantation.

- Arm IV: Patients receive idarubicin IV, ARA-C IV over 2 hours, and etoposide IV on days
1-3. Patients then undergo leukapheresis. Beginning on day 8, patients receive
filgrastim (G-CSF) SC daily until end of leukapheresis. Patients then receive oral
high-dose busulfan daily for 4 consecutive days. The following day, patients undergo
reinfusion of autologous PBSC. After blood count recovery, patients receive maintenance
IFN 3 times weekly for 8 weeks and then daily.

Patients are followed every 3 months for 3 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within 5 years.