Trial Information

Peripheral Blood Stem Cell Transplantation in Patients With Advanced Malignancies Eligible for Allogeneic Transplantation From Matched Related Donors: A Randomized Study of Cyclosporine/Methotrexate or Cyclosporine/T-Cell Depletion (CD34 Cell Selection) for GVHD Prophylaxis

OBJECTIVES: I. Demonstrate that the graft versus host disease (GVHD) prophylactic regimen
consisting of T-cell depletion and cyclosporine results in less toxicity than the control
regimen of methotrexate and cyclosporine in recipients of peripheral blood stem cell
transplants. II. Monitor safety of the two regimens in order to assure that the treatment
regimen dose not result in any increase in serious or unexpected toxicities, does not
compromise the efficacy of GVHD prophylaxis, and does not compromise the efficacy of the
disease therapy.

OUTLINE: This is a multicenter, controlled, randomized trial. Patients are assigned to high
or low risk groups and randomized to the control or treatment arms. Patients are stratified
by risk group and by site. Mobilization, apheresis, and successful cryopreservation of the
minimum number of CD34 cells for transplant has to be achieved prior to initiating
cytoreductive therapy. Following intensive cytoreductive therapy, patients receive either
unselected peripheral blood stem cells (PBSC) together with the control graft versus host
disease (GVHD) prophylaxis regimen or CD34+ cells isolated from PBSC with cyclosporine. In
the control group, GVHD prophylaxis consists of two drug therapies, cyclosporine and
methotrexate. The cyclosporine is administered first by IV continuous infusion and then
later orally, twice a day, in decreasing increments for 180 days. Methotrexate is
administered by IV on days 1, 3, 6, and 11. Cyclosporine is discontinued after day +180 if
there is no evidence of GVHD. In the treatment group, GVHD prophylaxis consists of T cell
depletion of the transplant product using the Isolex positive selection procedure (Isolex
selected CD34+ cells) and cyclosporine. The cyclosporine is administered at the same doses
and increments as in the control group. In cases where there still is acute or chronic GVHD,
the patient is given the appropriate salvage regimens. Patients are followed monthly for 6
months after transplant, and then for 2 years to monitor relapses.

PROJECTED ACCRUAL: There will be 200 patients accrued (100 in each arm) in this study.