Status:
COMPLETED
Fludarabine, Total-Body Irradiation, and Donor Stem Cell Transplant Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Chronic Myelogenous Leukemia
Lead Sponsor:
Fred Hutchinson Cancer Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Leukemia
Eligibility:
All Genders
Phase:
PHASE1
PHASE2
Brief Summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune sy...
Detailed Description
OBJECTIVES: Primary * Determine whether increasing the intensity of a nonmyeloablative conditioning regimen comprising fludarabine and total body irradiation allows achievement of a donor T-cell chi...
Eligibility Criteria
Inclusion
- DISEASE CHARACTERISTICS:
- Diagnosis of chronic myelogenous leukemia (CML), meeting 1 of the following criteria:
- First or second chronic phase
- Philadelphia chromosome-positive (Ph+) disease by cytogenetics or fluorescent in situ hybridization (FISH)
- First accelerated phase, meeting any of the following criteria:
- More than 10% but \< 30% myeloblasts and promyelocytes in bone marrow or peripheral blood
- Any additional clonal cytogenetic abnormalities
- Increasing splenomegally
- Extramedullary tumor
- WBC, platelet count, or hematocrit pertubations not controlled by therapy with hydroxyurea, interferon, or imatininb mesylate
- Persistent unexplained fever or bone pain
- Less than 5% blasts in marrow at time of transplant
- No blast crisis
- No other curative therapy exists
- Received prior imatinib mesylate AND meets ≥ 1 of the following criteria:
- Hematologic evidence of disease progression
- Lack of complete hematologic response after 3 months of treatment with imatinib mesylate
- Cytogenetic evidence of disease progression, defined as an increase in Ph+ cells or BCR/ABL-positive (BCR/ABL+) cells of \> 25%
- Lack of complete cytogenetic remission (no Ph+ cells by cytogenetic analysis or BCR/ABL+ cells by FISH) after 1 year of treatment with imatinib mesylate
- At least 65% Ph+ cells by cytogenetic analysis or BCR/ABL+ cells by FISH after 6 months of treatment with imatinib mesylate
- Less than 3-log reduction in BCR/ABL mRNA levels by quantitative polymerase chain reaction (Q-PCR) compared to a standard baseline level after 1 year of treatment with imatinib mesylate
- Molecular evidence of disease progression, defined as \> 1 log increase in BCR/ABL mRNA levels by Q-PCR, detected in 2 samples
- Experienced adverse events with imatinib mesylate treatment that would preclude further administration of the drug
- Patient refused further treatment with imatinib mesylate despite lack of disease progression
- Refused conventional myeloablative allogeneic stem cell transplantation OR at high risk for regimen-related toxicity due to pre-existing medical conditions (for patients \< 50 years of age)
- Unrelated donor available
- Matched at HLA-A, -B, -C, -DRB1, and -DQB1 by high-resolution typing
- A single allele\* disparity for HLA-A, -B, or -C allowed
- Negative anti-donor cytotoxic crossmatch
- Not a marrow donor NOTE: \*Patient and donor pairs homozygous at a mismatched allele (e.g., the patient is A\*0101 and the donor is A\*0201) are considered a two-allele mismatch and are not allowed
- No CNS involvement with disease that is refractory to intrathecal chemotherapy
- PATIENT CHARACTERISTICS:
- Age
- Any age
- Performance status
- Karnofsky 70-100%
- Lanksy 50-100% (for pediatric patients)
- Life expectancy
- Not specified
- Hematopoietic
- See Disease Characteristics
- Hepatic
- No fulminant liver failure
- No cirrhosis of the liver with evidence of portal hypertension
- No alcoholic hepatitis
- No esophageal varices
- No history of bleeding esophageal varices
- No hepatic encephalopathy
- No uncorrectable hepatic synthetic dysfunction evidenced by prolongation of PT
- No ascites related to portal hypertension
- No bacterial or fungal liver abscess
- No biliary obstruction
- No chronic viral hepatitis AND bilirubin \> 3 mg/dL
- No symptomatic biliary disease
- Renal
- Not specified
- Cardiovascular
- Ejection fraction ≥ 40%
- No cardiac failure requiring therapy
- No poorly controlled hypertension (i.e., blood pressure ≥ 150/90 mm Hg despite standard medication)
- Pulmonary
- DLCO ≥ 35% (corrected)
- No requirement for supplementary continuous oxygen
- Pulmonary nodules allowed at the discretion of the principal investigator
- Immunologic
- HIV negative
- No uncontrolled systemic infection
- No fungal infection with radiological progression after treatment with amphotericin B or active triazole for \> 1 month
- Other
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 12 months after completion of study treatment
- No other active malignancy except nonmelanoma skin cancer
- No prior localized malignancy at high risk (≥ 20%) of recurrence
- PRIOR CONCURRENT THERAPY:
- Biologic therapy
- See Disease Characteristics
- See Chemotherapy
- Chemotherapy
- See Disease Characteristics
- More than 3 weeks since prior cytotoxic chemotherapy
- Imatinib mesylate and interferon are not considered cytotoxic chemotherapy
- Endocrine therapy
- Not specified
- Radiotherapy
- Not specified
- Surgery
- Not specified
Exclusion
Key Trial Info
Start Date :
April 1 2005
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
November 1 2007
Estimated Enrollment :
75 Patients enrolled
Trial Details
Trial ID
NCT00119340
Start Date
April 1 2005
End Date
November 1 2007
Last Update
September 21 2010
Active Locations (3)
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1
Veterans Affairs Medical Center - Seattle
Seattle, Washington, United States, 98108
2
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
3
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024