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Chemotherapy and Biological Therapy With or Without Bone Marrow or Peripheral Stem Cell Transplant in Treating Patients With Chronic Myelogenous Leukemia
This study is ongoing, but not recruiting participants.
First Received: October 11, 2001   Last Updated: February 6, 2009   History of Changes
Sponsor: III. Medizinische Klinik Mannheim
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025402
  Purpose

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.


Condition Intervention Phase
Leukemia
 Biological: filgrastim
Biological: recombinant interferon alfa
Drug: busulfan
Drug: cyclophosphamide
Drug: cytarabine
Drug: etoposide
Drug: hydroxyurea
Drug: idarubicin
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
 Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
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

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood
Drug Information available for: Cyclophosphamide Busulfan Cytarabine hydrochloride Etoposide Idarubicin hydrochloride Idarubicin Interferon alfa-2a Etoposide phosphate Filgrastim Interferon alfa-n1 Hydroxyurea Cytarabine Interferons
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Survival [ Designated as safety issue: No ]
  • Frequency, time-point, and duration of hematologic and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCL-ABL-positive cells [ Designated as safety issue: No ]
  • Correlation of quality of hematological and cytogenetic remission with survival time [ Designated as safety issue: No ]
  • Course of the terminal phase [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time [ Designated as safety issue: No ]
  • Effect of early vs late high-dose therapy and autografting on feasibility, toxicity and survival times [ Designated as safety issue: Yes ]

Estimated Enrollment: 1000
Study Start Date: July 1997
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.

  • 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior interferon

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00025402

  Show 188 Study Locations
Sponsors and Collaborators
III. Medizinische Klinik Mannheim
Investigators
Study Chair: Ruediger Hehlmann, MD III. Medizinische Klinik Mannheim
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers: CDR0000068957, III-MK-CML-3A, EU-20118
Study First Received: October 11, 2001
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00025402     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
Philadelphia chromosome negative chronic myelogenous leukemia
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Interferon Type I, Recombinant
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Hydroxyurea
Hematologic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Leukemia
Therapeutic Uses
Growth Inhibitors
 Angiogenesis Modulating Agents
Alkylating Agents
Etoposide
Nucleic Acid Synthesis Inhibitors
Cytarabine
Interferon-alpha
Antisickling Agents
Neoplasms by Histologic Type
Hematologic Diseases
Growth Substances
Interferons
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Immunosuppressive Agents

ClinicalTrials.gov processed this record on November 22, 2009



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