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Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine

This study has been completed.
Miltenyi Biotec, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center. Identifier:
First received: January 7, 2008
Last updated: May 9, 2013
Last verified: May 2013

The purpose of this research study is to: (1) determine if the combination of low dose total body irradiation, low dose cyclophosphamide and the addition of fludarabine, and a serum to suppress the immune system can allow selected stem cells to take and grow; (2) determine if selected stem cells from the blood or marrow can take and not cause graft-versus-host disease (GvHD), and; (3) evaluate the side effects of the combination of low dose radiation and chemotherapy drugs used for these transplants.

Condition Intervention
Fanconi Anemia
Drug: Cyclophosphamide and Fludarabine

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine

Resource links provided by NLM:

Further study details as provided by Memorial Sloan Kettering Cancer Center.:

Primary Outcome Measures:
  • Incidence & quality of engraftment & hematopoietic reconstitution/Early transplant-related severe morbidity & mortality/Incidence & severity of acute & chronic GvHD/Quality of immune reconstitution following transplantation/Overall survival rate. [ Time Frame: 8 years ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: June 2001
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Cyclophosphamide and Fludarabine
Cyclophosphamide and Fludarabine

Detailed Description:

Patients with this disease are born with it and have a fragility of the genes (chromosomes) in all the cells of the body. The fragility of the chromosomes puts patients with FA at high risk for certain cancers. Patients with FA are especially at risk of having diseases of the blood and marrow systems. These include (1) aplastic anemia, a disease where there is a failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is represented by a clone of cells of the marrow that becomes "malignant" and stops making adequate numbers of blood cells (it is also called preleukemia.) The progression of the myelodysplastic syndrome will lead to (3) acute leukemia.

If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or leukemia standard treatment with medications or chemotherapy alone is not likely to cure these problems.

An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to provide you with marrow or blood stem cells from a healthy donor that can develop a normal blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic stem cell transplants have been done for the treatment of FA using stem cells from donors other than matched siblings, they have been associated with a high risk of rejection of the transplant and of a complication called graft-versus-host disease.

In order for the stem cells to grow and to kill leukemia cells, patients must receive chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients with Fanconi anemia, the standard preparation for stem cell transplantation has been the use of total body irradiation (at a lower dose because of the high risk of side-effects) and a chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has worked well with transplants from matched siblings, it was not enough in transplants from unrelated or cord blood donors and led to a high risk of rejection. In the last few years a medication called fludarabine was used successfully in transplants to give more immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low risks of rejection, and probably as importantly little risks of added side-effects. The addition of antithymocyte globulin to TBI, cyclophosphamide and fludarabine has made the chances of rejection very low.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:


  • Research participants must be have a diagnosis of Fanconi anemia (confirmed by mitomycin or diepoxybutane [DEB] chromosomal breakage testing).

Hematologic Diagnosis and Status:

  • Research participants must have one of the following hematologic diagnoses:

    • Severe Aplastic Anemia (SAA)/Severe Isolated Single lineage Cytopenia
    • Myelodysplastic Syndrome(MDS)
    • Acute leukemia.

HLA-compatible Unrelated volunteer donors:

  • Research participants who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B and DRB1 loci or who is mismatched at 1/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol.

HLA-mismatched Related donors:

  • Research participants who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
  • The donor must be healthy and willing and able (1) to receive a 5 day course of G-CSF and undergo 2 daily leukaphereses, or (2) to undergo general anesthesia and bone marrow donation. In order to undergo a Tcell depletion, a donor should be able to have a volume of 15 ml/Kg of the research participant's body weight harvested safely.

HLA-compatible Cord Blood Units:

  • Research participants who do not have a related HLA-matched donor but have an unrelated placental cord blood unit which matched at all A, B and DRB1 loci or who is mismatched at 1/6 or 2/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol.
  • Research participants may be of either gender or any ethnic background.
  • Research participants must have a Karnofsky adult, or Lansky pediatric performance scale status > 70%.
  • At the time of referral for transplantation, research participants must be in good clinical condition without co-existing medical problems that would significantly increase the risk of the transplant procedure. Research participants must be free of infections at the time of transplant. Research participants must have a life expectancy that is greater than 8 weeks.
  • Research participants must have adequate physical function measured by cardiac, Hepatic, Renal, Pulmonary.
  • Research participants must be available for follow-up evaluations at 30, 60, 180 days post BMT and yearly for 5 years.

Exclusion Criteria:

  • Active CNS leukemic involvement
  • Female research participants who are pregnant or breast-feeding
  • Active viral, bacterial or fungal infection
  • Research participant seropositive for HIV-I/II; HTLV -I/II
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00595127

United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center.
Miltenyi Biotec, Inc.
Principal Investigator: Farid Boulad, MD Memorial Sloan Kettering Cancer Center.
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan Kettering Cancer Center. Identifier: NCT00595127     History of Changes
Other Study ID Numbers: 01-062
Study First Received: January 7, 2008
Last Updated: May 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan Kettering Cancer Center.:
Stem Cell

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
Fludarabine phosphate
Alkylating Agents
Antimetabolites, Antineoplastic
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 February 25, 2015