Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
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.
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Procedure: hematopoietic stem cell transplantation
Drug: Mycophenolate Mofetil
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia|
- Graft failure [ Time Frame: From Day 1 to event ] [ Designated as safety issue: Yes ]graft failure = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy
- Incidence of Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation
|Study Start Date:||February 2000|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Patients with Fanconi Anemia receiving cyclophosphamide, fludarabine phosphate, antithymocyte globulin followed by matched sibling donor hematopoietic stem cell transplantation (HSCT). Patients also receive Mycophenolate Mofetil, methylprednisolone, cyclosporine and filgrastim.
Biological: anti-thymocyte globulin
30 mg/kg/day will be administered after MP on days -6, - 5, -4, -3 and -2.
Other Name: ATGAMDrug: cyclophosphamide
5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.
Other Name: CytoxanDrug: fludarabine phosphate
35 mg/m^2 intravenously (IV) on days -6 through -2.
Other Name: FludaraProcedure: hematopoietic stem cell transplantation
Bone marrow or umbilical cord blood infusion on day 0.
Other Name: stem cell transplantDrug: methylprednisolone
MP 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day +15 at which time it will be tapered 50% every 4 days to be discontinued by day +24 (i.e. MP 1 mg/kg/day on days +16-19, then 0.5 mg/kg/day on days +20-23, then discontinue). MP will be used as a premedication for ATG on day -6 to -2.
Other Name: MPDrug: filgrastim
Initiate G-CSF 5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count > or = 2.5 x 10^9/L
Other Name: G-CSFDrug: cyclosporine
cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper
Other Name: CSADrug: Mycophenolate Mofetil
Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours PO (to a maximum dose of 1 gram).
Other Name: MMF
- 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.
- 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.
- 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 continuing until day 100, followed by a taper. Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L.
After completion of study therapy, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00630253
|Contact: Margaret MacMillan, M.D.||firstname.lastname@example.org|
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Patricia Kleinke, RN 612-273-0857 Kleink1@fairview.org|
|Principal Investigator: Margaret MacMillan, M.D.|
|Principal Investigator:||Margaret L. MacMillan, MD||Masonic Cancer Center, University of Minnesota|