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
Trial Snapshot
- Phase
- Phase 3
- Sponsor
- Enrollment
- 1,000
- Locations
- 365
- Primary Endpoint
- Survival
Study Overview
Brief Summary
RATIONALE: Giving chemotherapy, such as hydroxyurea, cytarabine, idarubicin, and etoposide before a donor bone marrow transplant or 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. Interferon alfa may interfere with the growth of cancer cells and slow the growth of cancer. 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. It is not yet known whether chemotherapy is more effective with or without interferon alfa and/or bone marrow or stem cell transplant in treating patients with chronic myelogenous leukemia.
PURPOSE: This randomized phase III trial is studying chemotherapy and biological therapy to see how well it works compared with chemotherapy, biological therapy, and donor bone marrow transplant or autologous stem cell transplant in treating patients with chronic phase chronic myelogenous leukemia.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Primary Purpose
- Treatment
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Diagnosis of chronic myelogenous leukemia in chronic phase
- •Previously untreated
- •Patients negative for Philadelphia chromosome and BCR-ABL translocation must fulfill at least 1 of the following criteria:
- •Impaired health status with reduced exercise tolerance
- •Spleen-related symptoms in cases of splenomegaly
- •Weight loss greater than 10% in 6 months
- •Fever greater than 38.5 degrees C on 5 consecutive days
- •Clinically relevant bone pain
- •Leukocytosis greater than 5,000/mm^3
- •Thrombocytosis greater than 100,000/mm^3
- •PATIENT CHARACTERISTICS:
- •Performance status:
- •Not specified
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •See Disease Characteristics
- •Not specified
- •Not specified
- •No other concurrent malignancy that is likely to require treatment during study or that is likely to reduce life expectancy
- •No severe concurrent disease or other cause that would preclude study
- •Not pregnant
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •No prior interferon
- •Chemotherapy:
- •No prior chemotherapy
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •No prior radiotherapy
- •Not specified
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Survival
Correlation of quality of hematological and cytogenetic remission with survival time
Course of the terminal phase
Toxicity
Effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time
Effect of early vs late high-dose therapy and autografting on feasibility, toxicity and survival times
Frequency, time-point, and duration of hematologic and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCL-ABL-positive cells
Secondary Outcomes
No secondary outcomes reported