Spots Global Cancer Trial Database for Evaluating the Use of RFT5-dgA to Deplete Alloreactive Cells Prior to Haploidentical Stem Cell Transplantation

Study Description

Brief Summary: This study is designed to determine the number of donor lymphocytes that can be 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, and will result in a rate of Grade III/IV GVHD of \< / = 25%, to analyze immune reconstitution in these patients, and to measure their overall and disease free survival, at 100 days and at 1 year.

Detailed Description: 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 10cGy/min. 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).

Keywords

Eligibility

Minimum Age:

Eligible Ages: CHILD, ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: Yes

Locations

Contact Details

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