This phase I/II trial studies how well transplanting blood cells with chemotherapy work in treating patients with a high risk blood cancer that is in remission. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells and cancer cells. It may also help 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving filgrastim may stop this from happening. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Giving stem cells with chemotherapy and blinatumomab may work better in treating patients with blood cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT03849651.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. Determine the maximum effective dose for prophylactic CD45RA-depleted donor lymphocyte infusion (DLI) when given in the early post-engraftment period.
II. Assess the efficacy of T-cell receptor (TCR) alpha beta-depleted progenitor cell graft with additional memory T-cell DLI, plus selected use of blinatumomab, in haploidentical donor hematopoietic cell transplantation for hematologic malignancies as measured by 1 year event-free survival (EFS) (events = relapse, death).
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 neutrophil and platelet engraftment, malignant relapse, event-free survival per disease subgroups (e.g. acute lymphoblastic leukemia [ALL] versus [vs] acute myeloid leukemia [AML]), 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.
V. To measure and describe the pharmacokinetics of rabbit ATG in hematopoeitic cell transplantation (HCT) recipients on this study.
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 additional CD45RA-depleted DLI for recipients who have severe viral infections, disease recurrence or progression, or poor immune reconstitution.
III. Assess and record efficacy of CD45RA-depleted DLI for these conditions, and all adverse events that are related to CD45RA-depleted DLI.
OUTLINE: This is a phase I, dose-escalation study of CD45RA-depleted DLI followed by a phase II study.
Patients receive cyclophosphamide intravenously (IV) once daily (QD) on day -9, fludarabine phosphate IV QD on days -8 to -4, rabbit anti-thymocyte globulin IV daily over 2-6 hours on days -5 to -3, and melphalan IV QD on days -2 to -1. Patients also receive TCR alpha/beta positive (+) and CD19+ depleted hematopoietic progenitor cells IV on day 0 and may receive an additional dose on day 1. Patients receive filgrastim subcutaneously (SC) or IV daily for 2 consecutive days beginning on day 6. Beginning at least 2 weeks after engraftment, patients may receive CD45RA-depleted donor lymphocyte infusion IV. Patients with CD19+ malignancies also receive blinatumomab IV for 28 days beginning at least 1 week post-DLI.
After completion of study treatment, patients are followed up at days 21 and 100, at 1 year, and then annually for up to 10 years.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorBrandon Matthew Triplett
