TBI Dose De-escalation for Fanconi Anemia
This is a single arm, total body irradiation (TBI) trial. All patients will be prescribed TBI 300 cGy with the goal of evaluating secondary endpoints.
Procedure: Total Body Irradiation
Procedure: Bone Marrow Transplantation
Drug: Mycophenolate Mofetil
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation|
- Incidence of neutrophil recovery (absolute neutrophil count ≥500/µL for three consecutive days) . [ Time Frame: by day 42 ] [ Designated as safety issue: Yes ]
- 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 ]
|Study Start Date:||May 2006|
|Estimated Study Completion Date:||May 2016|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment with TBI
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac),10 mg/kg intravenously (IV)
Other Name: cytoxanDrug: Fludarabine
Day -5 through Day -2 prior to transplant; subjects will receive chemotherapy of Fludarabine via central line (i.e. Hickman or Broviac),35 mg/m^2 intravenous (IV)
Other Name: fludaraProcedure: Total Body Irradiation
total body irradiation (300 cGy) 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.
Other Name: Radiation Therapy, Therapeutic radiationProcedure: Bone Marrow Transplantation
A target of 5 * 10^6/kg and a minimum of 4 * 10^6 CD34+ cell/kg recipient weight will be collected by apheresis and used for transplant. In most cases this dose will be recovered in a single apheresis; however, a second or rarely third apheresis performed on the following days may be required to achieve the minimum dose.
Other Name: Stem Cell transplantationDrug: Mycophenolate Mofetil
Patients will receive MMF therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute graft-versus-host disease (GVHD). Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 * 10^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours by mouth(to a maximum dose of 1 gram).
Other Name: MMFDrug: Sirolimus
Sirolimus will be administered starting at day -3 with 8mg-12mg mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL by high-performance liquid chromatography (HPLC). Levels are to be monitored 3 times/week in the first 2 weeks, weekly until day +60, and as clinically indicated until day +100 post-transplantation. In the absence of acute GVHD sirolimus may be tapered starting at day +100 and eliminated by day +180 post-transplantation.
Other Name: Rapamycin
Study Treatment: Patients will receive voriconazole (antifungal therapy) by mouth beginning 1 month prior to conditioning therapy, if possible. 1) The subject is to receive total body irradiation (300 cGy) 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 and Cyclophosphamide via central line (i.e. Hickman or Broviac). Starting Day -3, patients will receive sirolimus therapy with a taper commencing on day +180 and also mycophenolate mofetil (MMF) through day +30 or for 7 days after engraftment, whichever day is later, if no acute graft-versus-host disease (GVHD). 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00352976
|Contact: Margaret L MacMillan, M.D.||email@example.com|
|United States, Minnesota|
|University of Minnesota Medical Center||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Margaret L MacMillan, M.D. 612-626-2778 firstname.lastname@example.org|
|Principal Investigator:||Margaret L MacMillan, M.D.||University of Minnesota Medical Center|