This trial studies how well donor stem cell transplantation with alpha/beta T cell and B cell depletion (partial Immune Cell Depletion) works in treating patients with hematologic malignancies. Alpha/beta T cell and B cell depletion is a new method of cell processing for stem cell transplants with an unrelated donor or partially matched related donor using the CliniMACS device. There is a higher rate of complications using cells from an unrelated or partially matched related donor. T cells within the donor cells may cause a complication called graft versus host disease, where the transplanted cells from a donor can attack the body's normal cells. Donated B cells can sometimes be infected with a virus (Epstein Bar Virus or EBV) which may result in the development of enlarged lymph nodes (lymphoproliferative disorder). Alpha/beta T cell and B cell depletion may reduce some of the complications of the transplant and decrease the time it takes for the new stem cells to grow in the body.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02323867.
PRIMARY OBJECTIVES:
I. Evaluate engraftment of patients receiving unrelated donor or partially matched related donor peripheral stem cells that have been alpha/beta T cell depleted and CD19+ B cell depleted using the CliniMACS device.
Ia. Evaluate primary non-engraftment.
Ib. Evaluate engraftment kinetics (time to absolute neutrophil count [ANC] > 500, platelets > 20 x 10^9/l).
II. Estimate incidence and extent of acute and chronic graft versus (vs.) host disease.
IIa. Overall acute graft versus host disease (GVHD) incidence.
IIb. Incidence of grade IV acute GVHD.
IIc. Incidence of chronic GVHD.
III. Assess incidence treatment-related mortality (TRM).
IV. Assess probability of one year leukemia free survival (LFS).
V. Assess tempo of immune reconstitution.
Va. Assess incidence of viral infections, including cytomegalovirus (CMV), adenovirus, human herpesvirus (HHV)6 and Epstein-Barr virus (EBV).
Vb. Assess tempo of lymphocyte reconstitution and recovery of T cell receptor excision circle (TREC)s.
VI. Pre-transplant evaluation will include killer cell immunoglobulin-like receptors (KIR) typing of the patient and donor.
OUTLINE: Patients receive 1 of 2 total body irradiation (TBI) conditioning regimens or a non-TBI conditioning regimen.
TBI CONDITIONING REGIMEN I: Patients receive thymoglobulin (ATG) intravenously (IV) on days -11 to -9 and undergo TBI over 6 fractions on days -8 to -6. Patients also receive thiotepa IV over 2 hours on days -5 to -4 and cyclophosphamide IV over 2 hours on days -3 to -2.
TBI CONDITIONING REGIMEN II: Patients receive ATG IV on days -9 to -7, thiotepa IV over 2 hours on days -7 to -6, cyclophosphamide IV over 2 hours on days -5 to -4, and undergo TBI over 6 fractions on days -3 to -1.
NON-TBI CONDITIONING REGIMEN: Patients receive busulfan IV on days -9 to -6, ATG IV on days -9 to -7, thiotepa IV over 2 hours on days -5 to -4, cyclophosphamide IV over 2 hours on days -3 to -2.
After all conditioning regimen, patients undergo hematopoietic stem cell transplantation (HCST) with alpha/beta T-cell/CD19+ B-cell-depleted unrelated or partially matched donor-derived allogeneic peripheral blood stem cells on day 0, and EBV positive patients receive rituximab on day 1.
Lead OrganizationChildren's Hospital of Philadelphia
Principal InvestigatorNancy Jane Bunin
