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

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center Identifier:
First received: April 24, 2006
Last updated: April 18, 2012
Last verified: April 2012

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.

Condition Intervention Phase
Fanconi Anemia
Drug: cyclophosphamide
Drug: cyclosporine
Drug: methotrexate
Procedure: allogeneic bone marrow transplantation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Dose-Finding Study for Cyclophosphamide as Conditioning Regimens for Bone Marrow Transplantation From Related Donors in Patients With Fanconi Anemia

Resource links provided by NLM:

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Conditioning-related toxicity [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
  • Graft rejection [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: June 1998
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Detailed Description:


  • 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.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • Not specified
  Contacts and Locations
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Please refer to this study by its identifier: NCT00317876

United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Universidade Federal do Parana
Curitiba, Parana, Brazil, 80.060-000
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Hans-Peter Kiem, MD Fred Hutchinson Cancer Research Center
  More Information

Responsible Party: Hans-Peter Kiem, MD, Fred Hutchinson Cancer Research Center Identifier: NCT00317876     History of Changes
Other Study ID Numbers: 1288.00  FHCRC-1288.00  CDR0000481264 
Study First Received: April 24, 2006
Last Updated: April 18, 2012
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
Fanconi anemia

Additional relevant MeSH terms:
Fanconi Anemia
Fanconi Syndrome
Anemia, Aplastic
Anemia, Hypoplastic, Congenital
Bone Marrow Diseases
DNA Repair-Deficiency Disorders
Genetic Diseases, Inborn
Hematologic Diseases
Kidney Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Renal Tubular Transport, Inborn Errors
Urologic Diseases
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on April 27, 2016