This phase I/II trial studies alpha-beta depleted T-cells and cyclophosphamide following stem cell transplant in treating patients with hematological malignancies. Giving chemotherapy and total-body irradiation before a donor hematopoietic tem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient’s immune cells and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing the T cells from the donor cells before the transplant may stop this from happening.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02193880.
PRIMARY OBJECTIVES:
I. To determine the safety of using the AB depleted (ABD) T-cell infusion following haploidentical (haplo) hematopoietic cell transplant (HCT) and post-transplant cyclophosphamide (CY). (Phase I)
II. To determine the efficacy of ABD T-cell infusion in improving progression-free survival (PFS). (Phase II)
SECONDARY OBJECTIVES:
I. To determine the incidence of graft-versus-host disease (GVHD) (acute and chronic) following haplo HCT followed by ABD T-cell infusion.
II. To determine the incidence of relapse following haplo HCT followed by ABD T-cell infusion.
III. To determine the cumulative risk of infection-related non-relapse mortality.
IV. To determine overall survival (OS) following haplo HCT followed by ABD T-cell infusion.
OUTLINE
PREPARATIVE REGIMEN:
MYELOID MALIGNANCIES: Patients receive fludarabine phosphate intravenously (IV) on days -6 to -3, busulfan IV on days -7, -5, -3, and -2, and undergo total-body irradiation (TBI) on day -1.
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) OR LYMPHOMAS =< 40 YEARS OLD: Patients undergo TBI on days -5 to -3 and receive cyclophosphamide IV on day -2.
ALL OR LYMPHOMAS > 40 YEARS OLD OR ANY AGE WITH MAJOR COMORBIDITIES: Patients receive fludarabine phosphate IV on days -6 to -3 and undergo TBI on days -2 and -1.
TRANSPLANT: All patients undergo haploidentical HCT on day 0.
ABD T-CELL INFUSION: Patients receive ABD T-cell infusion on day 7-9 of transplant.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV on days 3 and 4, mycophenolate mofetil IV over 2 hours or orally (PO) thrice daily (TID) on days 5-35 and tacrolimus IV continuously and switched to PO on days 5-100 with taper to day 180 in the absence of active GVHD.
After completion of study treatment, patients are followed up weekly up to day 100, monthly up to 1 year, and then periodically for 1 year thereafter.
Lead OrganizationUniversity of Alabama at Birmingham Cancer Center
Principal InvestigatorAyman Saad
