Clinical Trial: TBI Dose De-escalation for Fanconi Anemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation

Brief 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.

Detailed Summary: 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.
Sponsor: Masonic Cancer Center, University of Minnesota

Current Primary Outcome: Incidence of neutrophil recovery (absolute neutrophil count ≥500/µL for three consecutive days) . [ Time Frame: by day 42 ]

Original Primary Outcome: Incidence of neutrophil recovery (absolute neutrophil count ≥500/µL for three consecutive days) by day 42.

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • Incidence of grade ≥3 regimen related toxicity at day 100.
  • Incidence of secondary graft failure at 100 days.
  • Incidence of acute graft-versus-host disease (GVHD) at 100 days.
  • Incidence of chronic GVHD at one year.
  • Probability of survival at one year.
  • Incidence of infections at 100 days, 6 months and one year.
  • Immune reconstitution at 100 days, 6 month and one year.


Information By: Masonic Cancer Center, University of Minnesota

Dates:
Date Received: July 14, 2006
Date Started: May 18, 2006
Date Completion: December 2018
Last Updated: February 13, 2017
Last Verified: February 2017