This phase II trial studies how well donor progenitor cell and natural killer cell transplant works in treating younger patients with cancers of the blood that are at high risk of coming back or spreading. Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient’s immune system from rejecting the donor’s stem cells. When certain stem cells and natural killer 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. Sometimes the transplanted cells from a donor can make an immune response against the body’s normal cells. Removing the T cells from the donor cells before transplant may stop this from happening.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01807611.
PRIMARY OBJECTIVES:
I. To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus natural killer (NK) cell transplantation with total lymphoid irradiation (TLI) based conditioning regimen for high risk hematologic malignancy.
SECONDARY OBJECTIVES:
I. Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
II. Estimate incidence and severity of acute and chronic graft versus host disease (GVHD).
III. Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
EXPLORATORY OBJECTIVES:
I. Assess the relationship between pre-transplant minimal residual disease (MRD) with transplant outcomes.
II. Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) analysis, V-beta spectratyping, and lymphocyte phenotype and function.
III. Describe the use of cluster of differentiation (CD)45RA-depleted donor lymphocyte infusions (DLI) for recipients who have severe viral infections, disease recurrence or progression, or poor immune reconstitution.
IV. Assess and record efficacy of CD45RA-depleted DLI for these conditions, and all adverse events that are related to CD45RA-depleted DLI.
OUTLINE:
PREPARATIVE REGIMEN: Patients undergo TLI twice daily (BID) on day -9 and once daily (QD) days -8 and -7. Patients receive fludarabine phosphate intravenously (IV) QD on days -8 to -4, cyclophosphamide IV QD on day -6, thiotepa IV BID on day -3, and melphalan IV QD on days -2 and -1.
PROGENITOR CELLS: Patients receive allogeneic filgrastim-primed peripheral blood progenitor cells IV on days 0 and 1.
NK CELLS: Patients receive allogeneic CD56-positive CD3-negative natural killer cells IV on day 6.
After completion of study treatment, patients are followed up for 1 year.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorBrandon Matthew Triplett
