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Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myeloid Leukemia

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
busulfan
cyclophosphamide
cyclosporine
methotrexate
allogeneic bone marrow transplantation
peripheral blood stem cell transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia

Eligibility Criteria

15 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of chronic myeloid leukemia (CML) in chronic phase No chromosomal abnormalities other than a single Philadelphia chromosome (Ph) and less than 10% blasts in bone marrow and peripheral blood OR Diagnosis of CML in accelerated phase Must meet 1 of the following criteria: More than 10% and less than 30% myeloblasts plus promyelocytes in bone marrow or peripheral blood Major perturbations of WBC, platelet count, or hematocrit uncontrolled by chemotherapy with busulfan or hydroxyurea Progressive splenomegaly Extramedullary tumor Presence of any nonconstitutional cytogenetic abnormality in addition to a single Ph chromosome Persistent unexplained fever or bone pain Ph positive OR bcr/abl positive by reverse-transcriptase polymerase chain reaction or Southern blot No CML in blast phase PATIENT CHARACTERISTICS: Age: 15 to 65 Performance status: Not specified Life expectancy: At least 6 months based on any concurrent nonmalignant disease Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) (unless due to CML) SGOT and SGPT no greater than 2 times ULN (unless due to CML) Renal: Creatinine no greater than 1.4 mg/dL Cardiovascular: Cardiac ejection fraction at least 45% Pulmonary: DLCO at least 50% predicted Other: HIV negative Donor Entry Criteria: HLA-identical family member No psychological, physiological, or medical condition that would preclude harvest of peripheral blood stem cells or bone marrow HIV negative Hepatitis A, B, and C antigen negative Negative pregnancy test Age 12 years and over PRIOR CONCURRENT THERAPY: See Disease Characteristics

Sites / Locations

  • Fred Hutchinson Cancer Research Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
March 29, 2010
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002789
Brief Title
Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myeloid Leukemia
Official Title
A PHASE III RANDOMIZED STUDY COMPARING G-CSF MOBILIZED PERIPHERAL BLOOD STEM CELLS WITH MARROW AS THE SOURCE OF STEM CELLS FOR ALLOGENEIC TRANSPLANTS FROM HLA IDENTICAL, RELATED DONORS FOR THE TREATMENT OF CHRONIC MYELOID LEUKEMIA
Study Type
Interventional

2. Study Status

Record Verification Date
March 2010
Overall Recruitment Status
Completed
Study Start Date
May 1996 (undefined)
Primary Completion Date
September 2001 (Actual)
Study Completion Date
September 2001 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Stem cells that have been treated in the laboratory with filgrastim may prevent this from happening. Combining chemotherapy with bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known which treatment is more effective for chronic myeloid leukemia. PURPOSE: Randomized phase III trial to compare the effectiveness of donor peripheral stem cell transplantation with donor bone marrow transplantation in treating patients with chronic myeloid leukemia.
Detailed Description
OBJECTIVES: I. Compare the incidence of persistent cytogenetic or hematologic relapse in patients with chronic myeloid leukemia in chronic or accelerated phase treated with transplantation using filgrastim (G-CSF)-mobilized peripheral blood stem cells vs bone marrow from HLA-identical, related donors. II. Compare survival and nonrelapse mortality in patients treated with these regimens. III. Compare incidence and severity of acute and chronic graft versus host disease in patients treated with these regimens. IV. Compare hospitalization and treatment associated expenses for patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (15-39 vs 40-65), interval from diagnosis to transplantation (under 2 years vs 2 years or more, and permutations of patient and donor gender. Patients are randomized to one of two treatment arms. Arm I: Patients receive a preparative regimen comprising busulfan orally or IV 4 times daily on days -7 to -4 and cyclophosphamide IV on days -3 and -2. Allogeneic filgrastim (G-CSF)-mobilized peripheral blood stem cells are infused on day 0. Arm II: Busulfan and cyclophosphamide are administered as in arm I. Allogeneic bone marrow is infused on day 0. Patients receive graft-versus-host disease prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1-4 hours or orally every 12 hours on days -1 to 80 and then tapered. Patients are followed every 6 months for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of chronic myeloid leukemia (CML) in chronic phase No chromosomal abnormalities other than a single Philadelphia chromosome (Ph) and less than 10% blasts in bone marrow and peripheral blood OR Diagnosis of CML in accelerated phase Must meet 1 of the following criteria: More than 10% and less than 30% myeloblasts plus promyelocytes in bone marrow or peripheral blood Major perturbations of WBC, platelet count, or hematocrit uncontrolled by chemotherapy with busulfan or hydroxyurea Progressive splenomegaly Extramedullary tumor Presence of any nonconstitutional cytogenetic abnormality in addition to a single Ph chromosome Persistent unexplained fever or bone pain Ph positive OR bcr/abl positive by reverse-transcriptase polymerase chain reaction or Southern blot No CML in blast phase PATIENT CHARACTERISTICS: Age: 15 to 65 Performance status: Not specified Life expectancy: At least 6 months based on any concurrent nonmalignant disease Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) (unless due to CML) SGOT and SGPT no greater than 2 times ULN (unless due to CML) Renal: Creatinine no greater than 1.4 mg/dL Cardiovascular: Cardiac ejection fraction at least 45% Pulmonary: DLCO at least 50% predicted Other: HIV negative Donor Entry Criteria: HLA-identical family member No psychological, physiological, or medical condition that would preclude harvest of peripheral blood stem cells or bone marrow HIV negative Hepatitis A, B, and C antigen negative Negative pregnancy test Age 12 years and over PRIOR CONCURRENT THERAPY: See Disease Characteristics
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerry Radich, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States

12. IPD Sharing Statement

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Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myeloid Leukemia

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