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TBI Dose de-Escalation for Fanconi Anemia
This study is currently recruiting participants.
Verified by University of Minnesota, June 2008
Sponsored by: University of Minnesota
Information provided by: University of Minnesota
ClinicalTrials.gov Identifier: NCT00352976
  Purpose

This is a single arm, TBI trial. All patients will be prescribed TBI 300 cGy with the goal of evaluating secondary endpoints.


Condition Intervention Phase
Fanconi Anemia
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: ATG
Procedure: Total Body Irradiation
Procedure: Bone Marrow Transplantation
Phase II
Phase III

MedlinePlus related topics: Anemia Bone Marrow Transplantation
Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study
Official Title: Total Body Irradiation Dose De-Escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation

Further study details as provided by University of Minnesota:

Primary Outcome Measures:
  • Incidence of neutrophil recovery (absolute neutrophil count ≥500/µL for three consecutive days) . [ Time Frame: by day 42 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of grade ≥3 regimen related toxicity . [ Time Frame: at day 100 ] [ Designated as safety issue: Yes ]
  • Incidence of secondary graft failure at 100 days. [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Incidence of acute graft-versus-host disease (GVHD) [ Time Frame: at 100 days. ] [ Designated as safety issue: No ]
  • Incidence of chronic GVHD . [ Time Frame: at one year ] [ Designated as safety issue: No ]
  • Probability of survival . [ Time Frame: at one year ] [ Designated as safety issue: No ]
  • Incidence of infections . [ Time Frame: at 100 days, 6 months and one year ] [ Designated as safety issue: No ]
  • Immune reconstitution . [ Time Frame: at 100 days, 6 month and one year ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: May 2006
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cyclophosphamide
    Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac).
    Drug: Fludarabine
    Day -5 through Day -2, subjects will receive chemotherapy of Fludarabine via central line (i.e. Hickman or Broviac).
    Drug: ATG
    Day -5 through Day -2, subjects will receive chemotherapy of ATG via central line (i.e. Hickman or Broviac).
    Procedure: Total Body Irradiation
    total body irradiation with thymic shielding will be given six days before the stem cells are given (day -6). Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus.
    Procedure: Bone Marrow Transplantation
    Certain cancers can be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.
Detailed Description:

Study Treatment: 1. If the subject is to receive total body irradiation with thymic shielding, it will be given six days before the stem cells are given (day -6). 2. Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide, ATG, and Methylprednisone (a steroid used to help make sure the transplant "takes") via central line (i.e. Hickman or Broviac). On days -5 to -1, subjects will receive ATG and Methylprednisone. The methylprednisone will continue until about three weeks after transplant.3. Starting Day -3, subjects will be given cyclosporin A (CSA) therapy to help prevent graft-versus-host-disease. We will continue to give CSA until about six months after the transplant. 4. If the subject is receiving bone marrow or "peripheral" stem cells (cells collected from the donor's arm via a cell separator), on the day of transplantation, the stem cells taken from the donor will be put into a machine which will separate the lymphocytes (the cells that cause graft-versus-host disease [GVHD]) from the stem cells. If the subject is receiving an umbilical cord blood, the lymphocytes will not be removed because the risk of GVHD is not as high. Otherwise all patients will receive the same treatment. The stem cells are given as an infusion into the subject's existing catheter over 1-2 hours on day 0.5. On the day after transplant (day +1) subjects will be given G-CSF to stimulate the growth of the transplanted cells. 6. While receiving treatment and until the subject's blood counts recover he/she will have daily blood tests, and several bone marrow biopsies and aspirates. After recovery, subjects will be seen once a month for a health assessment and blood tests until at least 3 months after the cells have been infused. Additional blood tests or assessments may be done as medically indicated.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a ≤1 antigen mismatched HLA-A, B, DRB1 unrelated donor or ≤1 antigen mismatched related (non-HLA-matched sibling) or ≤2 antigen mismatched unrelated UCB donor.
  • Patients with FA must have aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype.
  • Adequate major organ function.
  • Women of child-bearing age must be using adequate birth control and have a negative pregnancy test.

Exclusion Criteria:

  • Available HLA-genotypically identical related donor.
  • Refractory anemia with excess blasts, or leukemia.
  • Active CNS leukemia at time of HSCT.
  • History of squamous cell carcinoma of the head/neck/cervix within 2 years of HSCT.
  • Pregnant or lactating female.
  • Prior radiation therapy that prevents further TBI.
  • Patients with advanced MDS (.i.e. RAEB or RAEBt or acute leukemia) will be excluded from this study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00352976

Contacts
Contact: Margaret L MacMillan, M.D. 612-626-2778 macmi002@umn.edu

Locations
United States, Minnesota
University of Minnesota Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Margaret L MacMillan, M.D.     612-626-2778     macmi002@umn.edu    
Sponsors and Collaborators
University of Minnesota
Investigators
Principal Investigator: Margaret L MacMillan, M.D. University of Minnesota Medical Center
  More Information

Responsible Party: University of Minnesota Medical Center ( MacMillan, Margaret L., MD )
Study ID Numbers: 0605M85788
Study First Received: July 14, 2006
Last Updated: June 16, 2008
ClinicalTrials.gov Identifier: NCT00352976  
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota:
Bone Marrow transplant
stem cell transplant
cord blood transplant
total body irradiation
thymic shielding

Study placed in the following topic categories:
Metabolic Diseases
Hematologic Diseases
Fanconi Anemia
Anemia
Cyclophosphamide
Fludarabine monophosphate
Genetic Diseases, Inborn
Fanconi's anemia
Anemia, Aplastic
Fludarabine
Bone Marrow Diseases
Aplastic anemia
Metabolic disorder

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
DNA Repair-Deficiency Disorders
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Anemia, Hypoplastic, Congenital
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009