Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02
N/A
44 Years
Both
Fanconi Anemia
Trial Information
Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02
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.
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Percent of Graft Failure
Outcome Description:
Graft failure = ANC <5 x 10^8/L by day 30.
Outcome Time Frame:
Day 30
Safety Issue:
No
Principal Investigator
Margaret L. MacMillan, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
2002LS014
NCT ID:
NCT00258427
Start Date:
March 2002
Completion Date:
July 2015
Related Keywords:
- Fanconi Anemia
- Fanconi anemia
- Anemia
- Fanconi Anemia
- Fanconi Syndrome
Name | Location |
|---|---|
| Masonic Cancer Center, University of Minnesota | Minneapolis, Minnesota 55455 |
