Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
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.
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Biological: Hematopoietic stem cell transplantation
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02|
- Percent of Graft Failure [ Time Frame: Day 30 ] [ Designated as safety issue: No ]Graft failure = ANC <5 x 10^8/L by day 30.
- Incidence of Acute and Chronic Graft-Versus-Host Disease [ Time Frame: Day 42 and 1 Year ] [ Designated as safety issue: No ]
- Incidence of Relapse [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
- Incidence of Major Infections [ Time Frame: Day 1 through End of Treatment ] [ Designated as safety issue: Yes ]
- Transplant-Related Toxicity [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
- Overall Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]cumulative proportion surviving
- Incidence of Chronic Graft-Versus-Host Disease [ Time Frame: Day 42 and 1 Year ] [ Designated as safety issue: No ]
|Study Start Date:||March 2002|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
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.
Biological: anti-thymocyte globulin
Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.
Other Name: ATGBiological: 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-CSFDrug: 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: BusulfexDrug: cyclophosphamide
10 mg/kg intravenously (IV) on Days -5 through -2.
Other Name: CytoxanDrug: fludarabine phosphate
35 mg/m^2 intravenously (IV) on Days -5 through -2.
Other Name: FludaraDrug: methylprednisolone
1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.
Other Name: MedrolBiological: 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
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00258427
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Timothy Krepski 612-273-2800 firstname.lastname@example.org|
|Principal Investigator: Margaret MacMillan, M.D.|
|Principal Investigator:||Margaret L. MacMillan, MD||Masonic Cancer Center, University of Minnesota|