This phase II trial studies how well blinatumomab and T cell depleted donor blood cell transplant work in treating children and young adults with hematologic cancer that has not responded (refractory) or has come back after a previous transplant (recurrent). White blood cells from donors may be able to kill cancer cells in patients with hematologic cancer. 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. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer cells to grow and spread. Giving blinatumomab after a blood cell transplant may destroy any remaining cancer cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02790515.
PRIMARY OBJECTIVE:
I. To estimate engraftment by day +30 post-transplant in patients who receive T cell receptor alpha beta (TCRalphabeta) depleted and cluster of differentiation (CD)45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation.
SECONDARY OBJECTIVES:
I. Assess the safety and feasibility of the addition of blinatumomab in the early post-engraftment period in patients with CD19+ malignancy.
II. Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
III. Estimate incidence and severity of acute and chronic graft versus host disease (GVHD).
IV. Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
EXPLORATORY OBJECTIVES:
I. 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.
II. Describe the use of CD45RA-depleted donor lymphocyte infusion (DLI) for recipients who have severe viral infections, disease recurrence or progression, or poor immune reconstitution. Assess and record efficacy of CD45RA-depleted DLI for these conditions, and all adverse events that are related to CD45RA-depleted DLI.
OUTLINE:
Patients receive rabbit anti-thymocyte globulin (ATG) intravenously (IV) daily on days -14, -13, and -12, cyclophosphamide IV once daily (QD) on day -9, fludarabine phosphate IV QD on days -8, -7, -6, -5, and -4, thiotepa IV twice daily (BID) on day -3. Patients receive melphalan IV QD on days -2 and -1, and rituximab IV on day -1. Patients receive sirolimus orally (PO) QD on day 0 until tapering beginning on day 42. Patients undergo TCR alpha beta depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation on days 0 and 1. Patients receive glycosylated recombinant human G-CSF AVI-014 subcutaneously (SC) or IV on days 6 and 7. Beginning 2 weeks post transplantation, patients who are CD19+ receive blinatumomab IV continuously for up to 21 days in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up at 21 and 100 days, and then annually for up to 10 years.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorBrandon Matthew Triplett
