Fanconi Anemia | Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia

Fanconi Anemia research study

What is the primary objective of this study?

RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for patients with high risk Fanconi's anemia. PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.

Who is eligible to participate?

Inclusion Criteria: - Patients must be <45 years of age with a diagnosis of Fanconi anemia with: - Biallelic BRCA2 mutations, or - Aplastic anemia, or advanced myelodysplastic syndrome (MDS) (MDS with ≥5% blasts), or acute leukemia who are ineligible for total body irradiation. Aplastic anemia is defined as having at least one of the following (with or without cytogenetic abnormalities): platelet count <20 * 10^9, - absolute neutrophil count (ANC) <5 * 10^8/L, - Hgb <8 g/dL / - Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors will be typed for HLA-A and B using serological level typing and for DRB1 using high resolution molecular typing. - Adequate major organ function including: - Cardiac: ejection fraction >45% - Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites, no cirrhosis) - Karnofsky performance status >70% or Lansky >50% - Women of child bearing potential must be using adequate birth control and have a negative pregnancy test. Exclusion Criteria: - Active CNS leukemia at time of HSCT. - Active uncontrolled infection within one week of hematopoietic stem cell transplant (HSCT). - Pregnant or lactating female. Donor Inclusion Criteria: - Donor must be in good health based on review of systems and results of physical examination. - Donor must have a normal hemoglobin, white count, platelet count and partial thromboplastin time (PTT), and a negative diepoxybutane (DEB) test. - HIV-NAT negative, HTLV-1, HTLV-2 negative, Hepatitis B and C negative. - Female donors of childbearing potential must have a negative pregnancy test. - Unrelated donors must agree to peripheral blood stem cell (PBSC) donation Donor Exclusion Criteria: - Donor is a lactating female.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Fanconi Anemia

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Biological:anti-thymocyte globulinGiven 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.

Biological:filgrastimgiven 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L)

Drug:busulfanBusulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old)

Drug:cyclophosphamide10 mg/kg intravenously (IV) on Days -5 through -2.

Drug:fludarabine phosphate35 mg/m^2 intravenously (IV) on Days -5 through -2.

Drug:methylprednisolone1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.

Biological:Hematopoietic stem cell transplantationInfused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

transplant in fanconi anemia patientsCytoreductive preparative regimen consisting of busulfan, cyclophosphamide, fludarabine phosphate, methylprednisolone, and antithymocyte globulin (ATG) followed by hematopoietic stem cell transplantation (HSCT) and post-transplant use of bone marrow-stimulating filgrastim.

Study Status


Start Date: March 26, 2002

Completed Date: January 2021

Phase: Phase 2

Type: Interventional


Primary Outcome: Percent of Graft Failure

Secondary Outcome: Incidence of Acute and Chronic Graft-Versus-Host Disease

Study sponsors, principal investigator, and references

Principal Investigator: Margaret MacMillan, MD

Lead Sponsor: Masonic Cancer Center, University of Minnesota


More information:

Discuss Anaemia