Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia

This study is currently recruiting participants.
Verified December 2013 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00258427
First received: November 22, 2005
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Fanconi Anemia
Biological: anti-thymocyte globulin
Biological: filgrastim
Drug: busulfan
Drug: cyclophosphamide
Drug: fludarabine phosphate
Drug: methylprednisolone
Biological: Hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Percent of Graft Failure [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
    Graft failure = ANC <5 x 10^8/L by day 30.


Secondary Outcome Measures:
  • Incidence of Acute and Chronic Graft-Versus-Host Disease [ Time Frame: Day 42 and 1 Year ] [ Designated as safety issue: No ]
  • Incidence of Relapse [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • Incidence of Major Infections [ Time Frame: Day 1 through End of Treatment ] [ Designated as safety issue: Yes ]
  • Transplant-Related Toxicity [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
  • Overall Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    cumulative proportion surviving

  • Incidence of Chronic Graft-Versus-Host Disease [ Time Frame: Day 42 and 1 Year ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: March 2002
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplant in Fanconi Anemia Patients
Hematopoietic stem cell transplantation (HSCT) in high risk patients with Fanconi Anemia (FA)- transplanted with related or unrelated CD34+ selected HSCT after Busulfan, Cytoxan, Fludarabine and Antithymocyte globulin.
Biological: anti-thymocyte globulin
Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.
Other Name: ATG
Biological: filgrastim
given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L)
Other Name: G-CSF
Drug: busulfan
Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old)
Drug: cyclophosphamide
10 mg/kg intravenously (IV) on Days -5 through -2.
Other Name: Cytoxan
Drug: fludarabine phosphate
35 mg/m^2 intravenously (IV) on Days -5 through -2.
Other Name: Fludara
Drug: methylprednisolone
1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.
Biological: Hematopoietic stem cell transplantation
Infused 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.
Other Name: HSCT

Detailed Description:

OBJECTIVES:

Primary

  • Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation.

Secondary

  • Determine the tolerability of mycophenolate mofetil in these patients.
  • Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.
  • Determine the incidence of major infections in patients with a history of major infections treated with this regimen.
  • Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen
  • Determine the probability of 1-year survival of patients treated with this regimen.

OUTLINE: Patients are stratified according to donor/recipient HLA type (identical vs other).

  • Cytoreductive combination chemotherapy: Patients receive busulfan intravenously (IV) over 2 hours twice daily on days -7 and -6 and cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes once daily on days -5 to -2.
  • Graft failure prophylaxis: Patients receive methylprednisolone IV twice daily on days -5 to 30 and anti-thymocyte globulin IV over 4-6 hours twice daily on days -5 to -1.
  • Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -3 to 100 (if patient has a matched sibling donor) or days -3 to 180 (if patient has another donor type). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 45.
  • Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT (using bone marrow or umbilical cord blood) on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 3 years.

  Eligibility

Ages Eligible for Study:   up to 44 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00258427

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Timothy Krepski    612-273-2800    tkrepsk1@fairview.org   
Principal Investigator: Margaret MacMillan, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Margaret L. MacMillan, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00258427     History of Changes
Other Study ID Numbers: 2002LS014, MT2002-02, 0202M18741
Study First Received: November 22, 2005
Last Updated: December 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
Fanconi anemia

Additional relevant MeSH terms:
Anemia
Fanconi Anemia
Fanconi Syndrome
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metabolism, Inborn Errors
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Fludarabine monophosphate
Lenograstim
Fludarabine
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Vidarabine
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on April 21, 2014