TBI Dose De-escalation for Fanconi Anemia
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|ClinicalTrials.gov Identifier: NCT00352976|
Recruitment Status : Recruiting
First Posted : July 17, 2006
Last Update Posted : December 5, 2017
|Condition or disease||Intervention/treatment||Phase|
|Fanconi Anemia||Drug: Cyclophosphamide Drug: Fludarabine Procedure: Total Body Irradiation Procedure: Bone Marrow Transplantation Drug: Mycophenolate Mofetil Drug: Sirolimus||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation|
|Actual Study Start Date :||May 18, 2006|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
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: cytoxan
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: fludara
Procedure: 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 radiation
Procedure: 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 transplantation
Drug: 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: MMF
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
- Incidence of neutrophil recovery (absolute neutrophil count ≥500/µL for three consecutive days) . [ Time Frame: by day 42 ]
- Incidence of grade ≥3 regimen related toxicity . [ Time Frame: at day 100 ]
- Incidence of secondary graft failure at 100 days. [ Time Frame: 100 days ]
- Incidence of acute graft-versus-host disease (GVHD) [ Time Frame: at 100 days. ]
- Incidence of chronic GVHD . [ Time Frame: at one year ]
- Probability of survival . [ Time Frame: at one year ]
- Incidence of infections . [ Time Frame: at 100 days, 6 months and one year ]
- Immune reconstitution . [ Time Frame: at 100 days, 6 month and one year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00352976
|Contact: Margaret L MacMillan, M.D.||firstname.lastname@example.org|
|United States, Minnesota|
|University of Minnesota Medical Center||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Margaret L MacMillan, M.D. 612-626-2778 email@example.com|
|Principal Investigator:||Margaret L MacMillan, M.D.||University of Minnesota Medical Center|