This phase II trial studies whether TCRαβ+CD3+/CD19+ depleted stem cells work at preventing graft versus host disease (GVHD) in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). An allogeneic HSCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. The donor cells sometimes attack the recipient’s healthy cells, resulting in GVHD. The severity of GVHD can be decreased when certain cells are removed from the stem cells before being given to the recipient. TCRαβ+CD3+/CD19+ depleted stem cells use the CliniMACS® device to remove alpha-beta CD3+/CD19+ cells. This may help prevent GVHD.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05968170.
PRIMARY OBJECTIVE:
I. To assess the incidence of severe GVHD following HSCT with allogeneic T-cell receptor (TCR) alpha/beta-positive T-lymphocyte-depleted peripheral blood stem cells (TCRαβ+CD3+/CD19+) depleted grafts, as determined by the presence of grade III-IV acute graft versus host disease (aGVHD) and/or chronic graft versus host disease (cGVHD) by Day+100 post-HSCT.
SECONDARY OBJECTIVES:
I. To assess the efficacy of TCRαβ+CD3+/CD19+ depleted HSCTs as measured by the engraftment of donor cells by Day 30 post-HSCT.
II. To assess the efficacy of TCRαβ+CD3+/CD19+ depleted HSCTs as measured by the incidence of transplant-related mortality at 1-year post-HSCT.
III. To assess the immune reconstitution following TCRαβ+CD3+/CD19+ depleted HSCTs as measured by the presence of expanded T-cell numbers and function at Day+180 post-HSCT.
SAFETY OBJECTIVES:
I. Assess the risk of microbial contamination in TCRαβ+CD3+/CD19+ depleted products from the CliniMACS® device.
II. Assess incidence of grade 4 or higher severe adverse events possibly, probably, or definitely attributed to the CliniMACS® αβ+CD3+/CD19+ Depletion Reagent System.
OUTLINE:
Patients receive transplant conditioning per local standard of care (SOC) 9-12 days prior to transplant. Patients then receive TCRαβ+CD3+/CD19+ depleted stem cells intravenously (IV) on day 0. Additionally, patients undergo blood sample collection throughout the study and bone marrow aspiration during follow-up. Patients also undergo echocardiography (ECHO) and may undergo bone marrow aspiration and/or lumbar puncture during screening.
After completion of study treatment, patients are followed up at days 30, 42, 100, 180, and 365.
Lead OrganizationChildren's Hospital Los Angeles
Principal InvestigatorNeena Kapoor
