Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Chemotherapy and Biological Therapy With or Without Bone Marrow or Peripheral Stem Cell Transplant in Treating Patients With Chronic Myelogenous Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	Any age	Other	III-MK-CML-3A EU-20118, NCT00025402

Objectives

1. 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.
2. Compare survival of patients with late-phase disease treated with high-dose cytarabine vs low-dose cytarabine followed by autografting and interferon alfa maintenance.
3. Compare survival of patients not responding cytogenetically to treatment with continued interferon alfa vs hydroxyurea.
4. 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.
5. Correlate the quality of hematological and cytogenetic remissions with survival time in patients treated with these regimens.
6. Compare the course of the terminal phase in patients treated with these regimens.
7. Compare the toxic effects of these regimens in these patients.
8. Determine the effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time in patients treated with these regimens.
9. Compare the effect of early vs late high-dose therapy plus autografting on feasibility, toxicity, and survival times in these patients.

Entry 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/mm³
  • Thrombocytosis greater than 100,000/mm³

Prior/Concurrent Therapy:

Biologic therapy:

• No prior interferon

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Patient Characteristics:

Age:

• Any age

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• 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

Expected Enrollment

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

Outcomes

Survival
Frequency, time-point, and duration of hematologic and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCL-ABL-positive cells
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

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.

Trial Contact Information

Trial Lead Organizations

III Medizinische Klinik Mannheim

Ruediger Hehlmann, MD, Protocol chair		Ph: 49-621-383-4115 Email: Ruediger.Hehlmann@med3.ma.uni-heidelberg.de

Registry Information
Official Title		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 Start Date		1997-07-22
Registered in ClinicalTrials.gov		NCT00025402
Date Submitted to PDQ		2001-08-02
Information Last Verified		2002-07-02

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