At a glance
ClinicalIndex Comparison Record- ✓Diagnosis of Fanconi anemia with aplastic anemia, MDS without excess blasts, or high-risk genotype (standard risk); or advanced MDS (≥5% blasts), acute leukemia, graft failure, severe infection history, renal disease (CrCl <40), or age >18 (high risk); or advanced MDS/acute leukemia post-initial HSCT (very high risk)
- ✓Cardiac ejection fraction >45%
- ✓Hepatic function with bilirubin, AST, ALT, ALP <5x normal
- ✓Karnofsky performance status >70% or Lansky >50 (if <16 years)
- ✕Available HLA-genotypically identical related donor (standard risk patients only)
- ✕Active central nervous system (CNS) leukemia at enrollment
- ✕History of squamous cell carcinoma of head, neck, or cervix within previous 2 years
- ✕Prior radiation therapy that precludes total body irradiation
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation
In Brief
A Phase 3 clinical trial evaluating Cyclophosphamide, Fludarabine, and 4 other interventions for Fanconi Anemia. Completed, enrolled 83 participants across 1 site.
Detailed Summary
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.
Study Details
Timeline
Interventions
Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac),10 mg/kg intravenously (IV)
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)
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.
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.
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).
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.