This phase II trial studies donor T cell depletion in preventing graft versus host disease (GVHD) in patients with blood cancer undergoing a donor stem cell transplant. Donor stem cell transplants, especially in the mismatched donor setting, are associated with increased risk for GVHD, a condition where the transplanted donor white blood cells attack your body’s normal tissues. Using a cell separation device may remove a subset of white blood cells (called alpha/beta T cells) from the donor product before the product is transplanted. This study is being done to assess whether this manipulation (called selective T cell depletion) will reduce the risk of GVHD and improve transplant outcome.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03717480.
PRIMARY OBJECTIVES:
I. To assess the day 100 severe acute graft versus host disease (GVHD)-free survival rate.
SECONDARY OBJECTIVES:
I. Grades II-IV and III-IV acute GVHD.
II. Chronic GVHD and moderate/severe chronic GVHD.
III. Chronic GVHD-free survival.
IV. Immune suppression-free survival.
V. Hematologic recovery (neutrophil and platelet engraftment).
VI. Immune reconstitution.
VII. Disease relapse.
VIII. Transplant-related mortality.
IX. Organ toxicity (e.g. sinusoidal obstruction syndrome [SOS]/veno-occlusive disease [VOD] and idiopathic pneumonia syndrome [IPS]).
X. Rates of infections (cytomegalovirus [CMV] and Epstein-Barr virus [EBV] reactivation).
XI. Disease-free and overall survival.
XII. Graft-versus-host disease and relapse free survival (GRFS).
OUTLINE:
PREPARATIVE REGIMEN: Patients are assigned to 1 of 2 regimens at the choice of treating physician.
REGIMEN I: Patients receive busulfan intravenously (IV) over 2 hours every 6 hours on days -9 to -7, melphalan IV over 30 minutes on days -6 to -5, and fludarabine IV over 30 minutes on days -6 to -2.
REGIMEN II: Patients undergo fractionated total body irradiation (TBI) thrice daily (TID) on days -10 to -7 for 11 doses. Patients also receive thiotepa IV over 4 hours on days -6 and -5, and fludarabine IV over 30 minutes on days -6 to -2.
TRANSPLANTATION: Patients receive allogeneic TCR alpha/beta-positive T-lymphocyte-depleted peripheral blood stem cells IV over 30-60 minutes on day 0.
After completion of study treatment, patients are followed up at day 100 and at 1 and 2 years.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorVincent Trien-Vinh Ho