Cyclophosphamide in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Fanconi's Anemia

Dose-Finding Study for Cyclophosphamide as Conditioning Regimens for Bone Marrow Transplantation From Related Donors in Patients With Fanconi Anemia

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's bone marrow. The donated bone marrow stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and methotrexate before or after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of cyclophosphamide in treating patients who are undergoing a donor bone marrow transplant for Fanconi's anemia.

Study Overview

• Status: Completed
• Conditions: Fanconi Anemia
• Intervention / Treatment: Drug: cyclophosphamide; Drug: methotrexate; Procedure: allogeneic bone marrow transplantation; Drug: cyclosporine; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Detailed Description

OBJECTIVES:

• Decrease the conditioning-related toxicity of cyclophosphamide without decreasing the engraftment rate to < 90% in patients undergoing allogeneic bone marrow transplantation for Fanconi's anemia.

OUTLINE: This is a multicenter, dose-finding study of cyclophosphamide.

• Nonmyeloablative conditioning regimen: Patients receive cyclophosphamide IV on days -5 to -2.

Cohorts of 5-10 patients receive decreasing doses of cyclophosphamide until the optimal dose (OD) is determined. The OD is defined as the dose at which ≥ 4 of 5 patients achieve engraftment and < 1 of 10 patients experiences dose-limiting toxicity.

• Allogeneic bone marrow transplantation (BMT): Patients undergo allogeneic BMT on day 0.
• Graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine orally or IV twice daily beginning on day -1 and continuing until day 49, followed by a taper on days 50-180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Parana
    • Curitiba, Parana, Brazil, 80.060-000
      • Universidade Federal do Paraná
• United States
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of Fanconi's anemia by chromosome fragility with a diepoxybutane (DEB) or mitomycin C test

  • Hemoglobin ≤ 8.0 g/dL, absolute granulocyte count ≤ 1,000/mm^3, or platelet count ≤ 50,000/mm^3
• No refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute leukemia
• HLA-identical related donor available

PATIENT CHARACTERISTICS:

• Glomerular filtration rate ≥ 30% predicted for age
• No liver disease (e.g., active hepatitis or moderate to severe portal fibrosis/cirrhosis by biopsy)
• No symptomatic cardiac insufficiency or symptomatic arrhythmia
• No other diseases that would severely limit the probability of survival
• No HIV seropositivity
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Conditioning-related toxicity	100 days post-transplant
Graft rejection	100 days post-transplant

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: June 1, 1998
• Primary Completion (ACTUAL): July 1, 2003

Study Registration Dates

• First Submitted: April 24, 2006
• First Submitted That Met QC Criteria: April 24, 2006
• First Posted (ESTIMATE): April 25, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 18, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Fanconi anemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Anemia; Fanconi Syndrome; Fanconi Anemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Antifungal Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Cyclophosphamide; Methotrexate; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 1288.00; FHCRC-1288.00; CDR0000481264 (REGISTRY: PDQ)