A Phase I Trial Evaluating The Use of RFT5-dgA to Deplete Alloreactive Cells PriorTo Haploidentical Stem Cell Transplantation
Patients will receive cytosine arabinoside (3g/m^2) IV every 12 hours for 6 doses starting
at 1400 hours on day -8. Cyclophosphamide (45mg/kg) will be given on Day -7 and Day -6.
MESNA (45mg/kg, divided into 5 doses) will be administered 15 minutes prior to each dose of
cyclophosphamide and 3, 6, 9 and12 hours after each dose of cyclophosphamide. Campath 1H IV
will be given on Days -3, -2 and -1. TBI, total dose 14.0 Gy will be delivered in 8
fractions of 1.75 Gy in two fractions per day beginning Day -4. The dose rate will be
Approximately thirty days following transplantation (day +30), the cryopreserved T cells
will be thawed and infused through a catheter line with normal saline.
This study will begin with a dose of T cells known not to cause GvHD even in haploidentical
recipients, even when the T cells administered have not first been allodepleted. A subset of
patients who achieved engraftment will be included in the dose escalation study of
allodepleted T-cells treated with RFT5-dgA. A continual reassessment method based on a
logistic dose-response curve with cohorts of size 2 will be employed to determine the MTD.
Cohorts of size 2 will be accrued beginning at dose level 1 and the dose-response curve is
estimated after toxicity outcome is observed to determine the recommended dose level for the
next patient cohort. Each and every patient will receive up to five additional injections of
T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or
higher GVHD, until total T cell numbers are > 1000/ul
Patients will be entered starting at level 1, according to the following doses:
Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose
level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4
(5 x 10^6 T cells/Kg).
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determining the number of donor lymphocytes given to recipients of haploidentical stem cell transplants after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin.
Malcolm Brenner, MB, PhD
Baylor College of Medicine
United States: Food and Drug Administration
|Methodist Hospital||Houston, Texas 77030|
|Texas Children's Hospital||Houston, Texas|