A Study to Determine the Safety and Efficacy of Using CD8-High Density Microparticles (CD8-HDM) to Deplete CD8+ Cells From Donor Lymphocyte Infusion in Order to Reduce Graft-versus-Host Disease (GvHD) Without Compromising an Anti-Leukemia Effect in Patients With Chronic Myeloid Leukemia Given HLA-Identical Sibling Peripheral Blood Stem Cell Transplants After Non-Myeloablative Conditioning
OBJECTIVES: I. Compare the incidence of acute graft versus host disease (GVHD) grades II-IV
and extensive chronic GVHD in chronic myeloid leukemia patients treated with purged donor
lymphocyte infusion (DLI) processed with CD8 high density microparticles (HDM) vs unpurged
DLI following nonmyeloablative, HLA identical sibling peripheral blood stem cell
transplantation. II. Compare the rates of complete cytogenetic, clinical, and hematologic
remission and mortality and GVHD in patients treated with these regimens. III. Determine the
efficacy of CD8 HDM in depleting greater than 95% of CD8+ cells in donor lymphocytes. IV.
Compare the safety and toxicity of these regimens in these patients.
OUTLINE: This is a randomized, double blind, multicenter study. Patients are stratified by
age (under 60 vs 60 and over) and center. Allogeneic peripheral blood stem cells (PBSC) are
harvested and selected for CD34+ cells on days 5-8. Nonmyeloablative conditioning: Patients
receive fludarabine IV over 30 minutes and cytarabine IV over 4 hours (beginning 4 hours
after the start of fludarabine infusion) on days -6 to -3 and idarubicin IV over 1-5 minutes
on days -6 to -4. Filgrastim (G-CSF) is administered subcutaneously daily beginning on day
-2 and continues until blood counts recover. Graft versus host disease prevention: Beginning
on day -2, patients receive tacrolimus IV continuously until oral dosing is tolerated.
Patients receive tacrolimus in combination with methotrexate on days 1, 3, and 6 after
completion of transplantation. Beginning 12 weeks after completion of transplantation, oral
tacrolimus is tapered and stopped over 4 weeks. Transplantation: Allogeneic PBSC are infused
on day 0. At 4 months posttransplantation, patients with residual Ph+ cells by cytogenetics
or FISH OR hematologic or clinical evidence of chronic myeloid leukemia AND without
symptomatic chronic graft versus host disease requiring immunosuppressive therapy are
randomized to 1 of 2 treatment arms: Arm I: Lymphocytes harvested from the original PBSC
donor are processed with the CD8 high density microparticle device to remove all or most
CD8+ cells. Patients receive CD8+ cell depleted donor lymphocyte infusion (DLI) IV over
15-30 minutes on the same day of collection. Arm II: Lymphocytes are harvested from the
original PBSC donor. Patients receive undepleted DLI IV over 15-30 minutes on the same day
of collection. Patients are followed at days 30, 60, 100, and 180, and then periodically
through year 5.
PROJECTED ACCRUAL: A maximum of 110 patients (55 per arm) will be accrued for this study
within 1 year.
Allocation: Randomized, Primary Purpose: Supportive Care
Gary J. Schiller, MD
Jonsson Comprehensive Cancer Center
United States: Federal Government