Clinical Trial: Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia

Brief Summary:

RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor stem cell transplant helps to remove the patient's cells to allow for the transplant cells to take and grow. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant and giving cyclosporine before and after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of cyclophosphamide, fludarabine, and antithymocyte globulin followed by donor stem cell transplant and to see how well it works in treating patients with Fanconi anemia.

Detailed Summary:

OBJECTIVES:

Primary

• To determine the probability of engraftment in patients with Fanconi anemia treated with cyclophosphamide, fludarabine phosphate, and antithymocyte globulin followed by HLA-genotypically identical sibling donor hematopoietic stem cell transplantation that is T-cell depleted.

Secondary

• To evaluate the incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
• To evaluate the incidence of regimen-related toxicity in these patients.
• To evaluate the 1-year survival of patients treated with this regimen.
• To evaluate the incidence of late secondary malignancies (e.g., squamous cell carcinoma of the head and neck or cervix) in patients treated with this regimen.

OUTLINE:

• Preparative cytoreductive therapy: Patients receive cyclophosphamide IV over 2 hours on days -6 to -3 and fludarabine phosphate IV over 30 minutes and anti-thymocyte globulin IV over 4-6 hours on days -6 to -2.
• T-cell depleted donor hematopoietic stem cell transplantation: Patients undergo T-cell depleted donor bone marrow or umbilical cord blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover.
• Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and
  Sponsor: Masonic Cancer Center, University of Minnesota
  

  Current Primary Outcome: Graft failure [ Time Frame: From Day 1 to event ]

  graft failure = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy
  
  
  

  Original Primary Outcome:

  • Graft failure
  • Mortality at day 100
  
  
  

  Current Secondary Outcome:

  • Incidence of Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: Day 42 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
  • Overall survival [ Time Frame: 1 Year ]

    The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.

    Overall survival will be defined as time from enrollment to date of death or censored at the date of last documented contact for patients still alive.

  • Incidence of Chronic Graft-Versus-Host Disease (GVHD) [ Time Frame: 1 Year ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
  • Transplant Related Deaths [ Time Frame: Day 100 ]
    In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation
  
  
  

  Original Secondary Outcome:

  • Incidence of acute graft-versus-host disease (GVHD) and chronic GVHD
  • Incidence of relapse
  • One-year survival
  
  
  Information By: Masonic Cancer Center, University of Minnesota
  

  Dates:
  Date Received: March 5, 2008
  Date Started: February 17, 2000
  Date Completion: June 2019
  Last Updated: March 28, 2017
  Last Verified: March 2017