Stem Cell Transplantation for Fanconi Anemia

This study has been terminated.
(Treatment with thymic shielding found safe, another study started.)
Sponsor:
Information provided by:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00167206
First received: September 9, 2005
Last updated: November 30, 2009
Last verified: November 2009
  Purpose

The purpose of this study is to determine whether thymic shielding during total body irradiation can be given and whether it will reduce the risk of infections in Fanconi Anemia patients undergoing alternate donor (not a matched sibling) stem cell transplants.


Condition Intervention Phase
Fanconi Anemia
Procedure: Hematopoietic Stem Cell Transplant
Procedure: Thymic Shielding During Radiation
Procedure: Total Body Irradiation
Drug: Cyclophosphamide, Fludarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of Thymic Shielding in Recipients of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Stem Cell Transplantation in Patients With Fanconi Anemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment [ Time Frame: Day 42 after hematopoietic cell transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Patients Who Exhibited Secondary Graft Failure [ Time Frame: Day 100 after hematopoietic cell transplant ] [ Designated as safety issue: No ]
  • Number of Patients With Acute Graft Versus-Host Disease (aGVHD) [ Time Frame: Day 100 after hematopoietic cell transplant ] [ Designated as safety issue: Yes ]
  • Number of Patients With Chronic Graft Versus-Host Disease (GVHD) [ Time Frame: 1 year after hematopoietic cell transplant ] [ Designated as safety issue: Yes ]
  • Number of Patients Who Exhibited Regimen-related Toxicity (RRT) [ Time Frame: 1 year after hematopoietic cell transplant ] [ Designated as safety issue: Yes ]
  • Immune Reconstitution - Mean Value (1 Year) [ Time Frame: 1 year post-transplant. ] [ Designated as safety issue: No ]
  • Immune Reconstitution - Mean Value (2 Years) [ Time Frame: at 2 years after transplant ] [ Designated as safety issue: No ]
  • Number of Patients Alive at 1 Year [ Time Frame: 1 year after transplant ] [ Designated as safety issue: No ]
  • Number of Patients Alive at 2 Years [ Time Frame: 2 years after transplant ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: March 2004
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HSCT Patients
Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
Procedure: Hematopoietic Stem Cell Transplant
Bone marrow failure may 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. 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.
Other Name: Bone Marrow Transplant
Procedure: Thymic Shielding During Radiation
protecting the thymus during total body radiation (450 cGy administered)
Other Name: TBI
Procedure: Total Body Irradiation
Six days before the stem cells are given (day -6), subjects will receive total body irradiation with thymic shielding. 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.
Other Name: Radiation Therapy, Therapuetic Radiation
Drug: Cyclophosphamide, Fludarabine
Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide via central line
Other Name: Cytoxan, Fludara

Detailed Description:

All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be less than (<) 18 years of age with a diagnosis of Fanconi anemia.
  • Patients must have an HLA-A, B, DRB1 identical unrelated donor or less than or equal to (≤)1 antigen mismatched related (non-HLA-matched sibling) or <1 antigen mismatched unrelated UCB donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing.
  • Patients with FA must have aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below.

    • Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions
    • Platelet count <20 x 10^9/L
    • ANC <5 x 10^8/L
    • Hgb <8 g/dL
    • Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies
    • High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)
  • Adequate major organ function including

    • Cardiac: ejection fraction greater than (>)45%
    • Hepatic: bilirubin, AST/ALT, ALP <2 x normal
    • Karnofsky performance status >70% or Lansky performance status >50%
  • 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
  • History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies)
  • Refractory anemia with excess blasts, or leukemia
  • Active central nervous system (CNS) leukemia at time of hematopoietic cell transplant (HCT)
  • History of squamous cell carcinoma of the head/neck/cervix within 2 years of HCT
  • Pregnant or lactating female
  • Prior radiation therapy preventing use of total body irradiation (TBI) 450 centigray (cGy)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00167206

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Margaret MacMillan, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: MacMillan, Margaret L., MD, Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00167206     History of Changes
Other Study ID Numbers: 0312M54991, MT2003-18
Study First Received: September 9, 2005
Results First Received: July 7, 2009
Last Updated: November 30, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
Stem Cell Transplant
Thymic Shielding
Total Body Irradiation
Chemotherapy

Additional relevant MeSH terms:
Anemia
Fanconi Anemia
Fanconi Syndrome
Anemia, Aplastic
Anemia, Hypoplastic, Congenital
Bone Marrow Diseases
DNA Repair-Deficiency Disorders
Genetic Diseases, Inborn
Hematologic Diseases
Kidney Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Renal Tubular Transport, Inborn Errors
Urologic Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014