This phase I trial studies the side effect of intentional graft rejection using recipient white blood cell infusion following donor stem cell transplant and to see how well it works in treating patients with non-Hodgkin lymphoma, Hodgkin lymphoma, or multiple myeloma that is not responding to treatment or has returned after a period of improvement. One risk of a stem cell transplant is that the donated stem cells do not grow in the recipient. This is called graft rejection. Graft rejection occurs when the infection-fighting system (immune system) of the recipient recognizes the donor stem cells as being different and destroys them. In most stem cell transplants the goal is to try to prevent graft rejection so that the donor’s cells grow and produce new blood cells; however, the reaction between the recipient’s cells and the donor’s cells that causes graft rejection may be associated with an anti-cancer effect. Recipient leukocyte infusion causes the immune system to react against the donor’s cells and reject the transplant. Intentional graft rejection using recipient leukocyte infusion after a donor stem cell transplant may lead to regression of cancer cells in patients with relapsed or refractory non-Hodgkin lymphoma, Hodgkin lymphoma, or multiple myeloma.
Additional locations may be listed on ClinicalTrials.gov for NCT00909948.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To study the feasibility of a minimal, non-myeloablative conditioning regimen achieving initial mixed chimerism of human leukocyte antigen (HLA)-mismatched related donor cluster of differentiation 34+ (CD34+) hematopoietic stem cells without graft versus host disease (GVHD).
II. To determine the safety including acute GVHD and transplant related mortality at =< 100 days of this regimen when followed by infusion of recipient leukocytes (RLI) to induce deliberate rejection of the donor graft.
SECONDARY OBJECTIVES:
I. To evaluate the incidence of acute and chronic GVHD.
II. To evaluate the incidence of loss of donor grafts.
III. To evaluate progression-free and overall survival.
IV. To evaluate antitumor responses following this transplant strategy.
OUTLINE: Patients are assigned to 1 of 2 treatment regimens.
REGIMEN A:
CONDITIONING REGIMEN: Patients undergo total body irradiation (TBI) on day 0.
STEM CELL TRANPLANT: Patients undergo non-myeloablative allogeneic peripheral blood stem cell transplantation 4-6 hours after TBI on day 0 and on day 1 if necessary.
GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) twice daily (BID) on day -1 to day 21 with a taper to day 35 and mycophenolate mofetil PO or intravenously (IV) BID beginning 4-6 hours after the stem cell infusion on day 0 to day 21.
RECIPIENT LEUKOCYTE INFUSION: Patients with mixed chimerism and no evidence of clinical GVHD receive RLI between days 38-40. After at least 2 weeks, patients with evidence of persistent donor chimerism receive a second RLI.
REGIMEN B:
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
STEM CELL TRANSPLANT: Patients undergo non-myeloablative allogeneic peripheral blood stem cell transplantation 4-6 hours after TBI on day 0 and day 1 if necessary.
GVHD PROPHYLAXIS: Patients receive cyclosporine PO BID on day -1 to day 21 with a taper to day 35 and mycophenolate mofetil PO or IV BID beginning 4-6 hours after the stem cell infusion on day 0 to day 21.
RECIPIENT LEUKOCYTE INFUSION: Patients with mixed chimerism and no evidence of clinical GVHD receive RLI between days 38-40. After at least 2 weeks, patients with evidence of persistent donor chimerism receive a second RLI.
After completion of study treatment, patients are followed up at 6, 12, and 24 months.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorBimalangshu Ranjan Dey
