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Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia

This study is currently recruiting participants.
Verified December 2017 by Masonic Cancer Center, University of Minnesota
Sponsor:
ClinicalTrials.gov Identifier:
NCT00258427
First Posted: November 24, 2005
Last Update Posted: December 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
November 22, 2005
November 24, 2005
December 5, 2017
March 26, 2002
January 2018   (Final data collection date for primary outcome measure)
Percent of Graft Failure [ Time Frame: Day 30 ]
Graft failure = ANC <5 x 10^8/L by day 30.
Not Provided
Complete list of historical versions of study NCT00258427 on ClinicalTrials.gov Archive Site
  • Incidence of Acute and Chronic Graft-Versus-Host Disease [ Time Frame: Day 42 and 1 Year ]
  • Incidence of Relapse [ Time Frame: 1 Year ]
  • Incidence of Major Infections [ Time Frame: Day 1 through End of Treatment ]
  • Transplant-Related Toxicity [ Time Frame: Day 100 ]
  • Overall Survival [ Time Frame: 1 Year ]
    cumulative proportion surviving
  • Incidence of Chronic Graft-Versus-Host Disease [ Time Frame: Day 42 and 1 Year ]
Not Provided
Not Provided
Not Provided
 
Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Fanconi Anemia
  • 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)
    Other Name: Busulfex
  • 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.
    Other Name: Medrol
  • 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
Experimental: transplant in fanconi anemia patients
Cytoreductive 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.
Interventions:
  • Biological: anti-thymocyte globulin
  • Biological: filgrastim
  • Drug: busulfan
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Drug: methylprednisolone
  • Biological: Hematopoietic stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
25
January 2019
January 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
up to 44 Years   (Child, Adult)
No
Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org
United States
 
 
NCT00258427
2002LS014
MT2002-02 ( Other Identifier: Blood and Marrow Transplantation Program )
0202M18741 ( Other Identifier: IRB, University of Minnesota )
Yes
Not Provided
Not Provided
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Margaret MacMillan, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP