Fludarabine, Total-Body Irradiation, and Donor Stem Cell Transplant Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Chronic Myelogenous Leukemia

NCT00119340 | Completed Phase 1

• 3 other identifiers: 1939.00FHCRC-1939.00CDR0000432959
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

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 system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects and best dose of fludarabine, total-body irradiation, and donor stem cell transplant followed by cyclosporine and mycophenolate mofetil and to see how well they work in treating patients with chronic myelogenous leukemia.

Conditions

Leukemia

Keywords

accelerated phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia

Outcome Measures

Primary Outcomes (4)

• Increase number of patients with donor T-cell chimerism from > 40% to 90% on day 28 post-transplant

• Reduce graft rejection rate to < 10% day 84 post-transplant

• Maintain acute graft-vs-host disease (GVHD) incidence of 10%

• Maintain nonrelapse mortality incidence of < 15% on day 200 post-transplant

Secondary Outcomes (3)

• Rate of complete cytogenetic remission

• Probability of actuarial disease-free survival

• Pharmacokinetics

Interventions

cyclosporine DRUG

fludarabine phosphate DRUG

mycophenolate mofetil DRUG

peripheral blood stem cell transplantation PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Veterans Affairs Medical Center - Seattle

Seattle, Washington, 98108, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase

Interventions

Cyclosporine; fludarabine phosphate; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Brenda Sandmaier, MD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 12, 2005
• First Posted: July 13, 2005
• Study Start: April 1, 2005
• Study Completion: November 1, 2007
• Last Updated: September 21, 2010

Record last verified: 2010-09

Locations

US (3)