Trial Information

PROSPECTIVE CONTROLLED STUDY FOR THE OPTIMIZATION OF THERAPY IN CHRONIC MYELOID LEUKEMIA (CML): MULTICENTRIC STUDY FOR THE EVALUATION OF INTERFERON ALPHA VS ALLOGENIC BM TRANSPLANTATION WITH CHEMOTHERAPY IN CML

OBJECTIVES:

- Compare the duration of chronic phase chronic myelogenous leukemia (CML) and survival
of these patients treated with standard remission induction comprising hydroxyurea (HU)
and interferon alfa (IFN-A), followed by allogeneic bone marrow transplantation and
consolidation comprising HU and IFN-A vs cytarabine and idarubicin.

- Compare the frequency of hematologic and cytogenetic remission (including elimination
of Philadelphia-positive and/or BCR/ABL-positive chromosome abnormalities), time to
remission, and duration of remission in patients treated with these regimens.

- Correlate the quality of hematologic and cytogenetic remission with the survival of
patients treated with these regimens.

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

- Compare the disease progression in patients treated with these regimens.

- Correlate the duration of chronic phase CML and survival with prognostic criteria and
the significance of normal vs subnormal leukocyte counts in patients treated with these
regimens.

- Compare the survival of patients without a suitable allogeneic bone marrow donor
treated with autologous bone marrow transplantation as consolidation therapy vs
consolidation and maintenance chemotherapy regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center, eligibility for allogeneic bone marrow transplantation (Allo-BMT) (yes
vs no), donor availability (sibling vs unrelated vs none), and risk status (high vs low).

Induction therapy

- Patients receive induction therapy comprising oral hydroxyurea (HU) until WBC falls
below 10,000/mm^3 and interferon alfa (IFN-A) subcutaneously (SC) daily beginning after
WBC reduction and continuing in order to maintain WBC between 2,000-4,000/mm^3 and
platelet count greater than 50,000/mm^3. If WBC is 10,000/mm^3 or greater on IFN-A
alone, then HU must be restarted. Patients with disease progression and no anti-IFN
antibody also receive cytarabine (ARA-C) SC for 15 days a months. Patients who develop
disease progression while receiving ARA-C and IFN-A are taken off study.

- Patients who are eligible for Allo-BMT, have a sibling donor, and are age 55 and under
receive induction therapy for a maximum of 1 year and then proceed to regimen B.
Patients who are eligible for Allo-BMT, have an unrelated donor, and are age 45 and
under receive induction therapy for 12-18 months. Those patients with cytogenetic
remission receive induction therapy for up to 2 years and then proceed to regimen B.
Those patients without cytogenetic remission proceed directly to regimen B. Patients
who are ineligible for Allo-BMT, but are eligible for autologous BMT (AuBMT) or
peripheral blood stem cell transplantation (PBSCT) receive induction therapy for a
maximum of 1 year and then proceed to regimen C. Patients who are ineligible for
Allo-BMT and achieve hematologic complete remission (CR) within 3 months receive
induction therapy for 18 months. Those patients with cytogenetic remission proceed
directly to regimen A. Those patients without cytogenetic remission proceed to
randomization on regimen B. Patients who are ineligible for Allo-BMT and fail to
achieve hematologic CR within 9 months proceed to randomization on regimen B. All other
patients who are ineligible for Allo-BMT receive induction therapy for 1 year. Those
patients with cytogenetic remission proceed to regimen A. Those patients without
cytogenetic remission proceed to randomization on regimen B.

Consolidation/maintenance therapy

- Patients are assigned to 1 of 3 regimens.

- Regimen A: Patients continue to receive IFN-A as in induction therapy in the absence of
disease progression.

- Regimen B: Patients receive conditioning therapy comprising busulfan for 4 days and/or
total body irradiation, followed by Allo-BMT. Patients are then randomized to 1 of 2
treatment arms.

- Arm I: Patients receive consolidation therapy comprising HU and IFN-A as in
induction therapy.

- Arm II: Patients receive consolidation therapy comprising ARA-C SC every 12 hours
on days 1-5 and idarubicin (IDA) IV on days 3 and 4 (and day 5 for patients with
responding disease). Consolidation therapy continues every 2 months for a total of
3 courses. When blood counts recover, patients receive maintenance therapy
comprising IFN-A and ARA-C (if needed) as in induction therapy.

- Regimen C: Patients receive IDA and ARA-C as in arm II. Patients then undergo AuBMT or
PBSCT.

Patients are followed every 3-6 months for at least 4 years.

PROJECTED ACCRUAL: Approximately 750 patients will be accrued for this study within 5 years.