This phase I/II studies the side effects and effect of a donor stem cell transplant with alpha/beta T cell and CD19+ B cell depleted stem cells works in treating patients with hematological malignancies and non-malignant disorders. Stem cells or "mother" cells are the source of normal blood cells and lead to recovery of blood counts after bone marrow transplantation. Sometimes the transplanted cells from a donor can attack 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. A donor stem cell transplant with alpha/beta T cell and CD19+ B cell depleted stem cells may reduce some of the complications of the transplant and decrease the time it takes for the new stem cells to establish a new immune system.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05236764.
PRIMARY OBJECTIVES:
I. Cumulative incidence of both neutrophil and platelet engraftment by day 42 post hematopoietic cell transplant (HCT) as a composite endpoint.
II. Cumulative incidence of grade III or higher acute graft versus-host disease (aGVHD) by day 100 post HCT.
SECONDARY OBJECTIVES:
I. Cumulative incidence of transplant-related mortality (TRM) at day 100 and day 365.
II. Overall survival (OS) up to one year post HCT.
III. Cumulative incidence of chronic graft versus-host disease (GVHD) up to 2-years post-HCT.
EXPLORATORY OBJECTIVES:
I. Feasibility of using the automated CliniMACS system to produce a graft with defined cell composition.
II. Incidence of viral reactivations – defined as detectable viral load by peripheral blood polymerase chain reaction (PCR) – and/or symptomatic infections up to one year post HCT.
III. For patients with hematological malignancies, complete donor chimerism within 30 days from engraftment.
IV. T-, B- and natural killer (NK)-cell subset analysis at day 30, 60, 100, 180 and 365 post-HCT.
V. Recent thymic emigrants (RTE) at day 100, provided absolute lymphocytes count (ALC) is > 200 x10e9/L, then at day 180 and 365.
VI. T-cell repertoire analysis by flow cytometry at day 180 post-transplant.
VII. Proportion of alpha/beta versus gamma/delta T-cell receptor positive cells present at day 30, 60, 100, 180 and 365 post-HCT.
VIII. NK screening subset at day 30, 60, 100, 180 and 365 post-HCT.
IX. Extended NK cell phenotype at day 30, 60, 100, 180 and 365 post-HCT.
OUTLINE:
Patients receive a myeloablative or reduced intensity conditioning regimen at the discretion of the treating physician. Patients receive rituximab intravenously (IV) on day -1. Patients then undergo allogeneic hematopoietic stem cell transplant by receiving alpha/beta T cell and CD19+ B cell depleted stem cells IV on day 0. Patients undergo chest x-ray or computed tomography (CT) during screening. Patients also undergo echocardiography (ECHO), bone marrow biopsy and aspiration, and lumbar puncture throughout the trial.
After completion of study treatment, patients are followed up at day 28, weekly until day 100, monthly through month 11 and then annually until year 5.
Lead OrganizationBaylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Principal InvestigatorErin Andrea Morales Ubico
