This phase I trial studies the safety, side effects, and effectiveness of giving genetically engineered cells called CD45RA-depleted CD19-chimeric antigen receptor (CAR) T cells after a stem cell transplantation by a partially matched family member to children with CD19-positive blood cancers that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). In this trial, 2 different types of donor cells are given to patients. The first type are stem cells that are selected to remove the cells that can cause bad side effects. T-cells are a type of white blood cell that help us fight against infections or cancer. A certain type of T-cell called TCRαβ T cells are removed before giving the rest of the blood making product to patients. The T-cell receptor (TCR) is a molecule that is found only on T-cells. About 95% of all T-cells have TCRαβ on their cells, and these cells are removed prior to infusion. These cells are removed to lower the risk of developing a condition after the donor cell infusion called graft-versus-host disease (GVHD). The second type of donor cells are also T-cells. There are two type of T-cells, memory T cells and naïve T cells. The naïve cells are removed because they are more likely to cause GVHD, and memory cells are kept because they are less likely to cause GVHD. Scientists have found a way to genetically modify memory T cells to insert a CAR into the patient's T-cells, which allows these T-cells to find and destroy the cancer. These cells are called CD45RA-depleted CD19 CAR T cells. In addition, chemotherapy is given before the donor cells helps kill cancer cells in the body and helps make room in the patient's bone marrow for new stem cells to grow. Giving CD45RA-Depleted CD19-CAR T Cells after TCRαβ+ depleted donor stem cell transplantation may be a safe and effective treatment for children with relapsed/refractory CD19-positive blood cancers.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07257419.
Locations matching your search criteria
United States
Tennessee
Memphis
Saint Jude Children's Research HospitalStatus: Approved
Contact: Swati Naik
Phone: 901-595-3300
PRIMARY OBJECTIVE;
I. To assess the safety and feasibility of combining allogeneic CD19-CAR CD45RA-negative T-cells (CD19-CAR [Memory] [Mem] T cells) after TCRαβ+/CD19-depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
SECONDARY OBJECTIVES:
I. Estimate 1-year post-transplant overall survival, event-free survival, and graft-versus-host disease (GVHD)-free relapse-free survival (GRFS).
II. Estimate cumulative incidence of engraftment, acute and chronic GVHD, and immune-related adverse events, including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS).
EXPLORATORY OBJECTIVES:
I. To determine the expansion, persistence, phenotype, repertoire, and functional state of both, infused allogeneic cells from the graft and CD19-CAR(Mem) T-cells.
II. To characterize the cytokine profile in the peripheral blood after infusion of CD19-CAR (Mem) T-cells.
III. To characterize incidence and mechanisms of relapse post-therapy by studying leukemic blasts and immune cell signatures.
OUTLINE:
DONORS: Donor participants undergo apheresis over 3-8 hours on study. Donor participants also receive filgrastim subcutaneously (SC) once daily (QD) or twice daily (BID) on days -5 to -1 or days -5 to 0, and then undergo an additional apheresis procedure over 3-8 hours on day -1 (days -1 and 0 if needed).
CONDITIONING: Patients receive lapine T-lymphocyte immune globulin (rabbit ATG) intravenously (IV) over 2-6 hours on days -12, -11, and -10, cyclophosphamide IV QD on day -9, fludarabine IV QD on days -8, -7, -6, -5, and -4, thiotepa IV BID on day -3, and melphalan IV QD on days -2 and -1 in the absence of disease progression or unacceptable toxicity.
TRANSPLANT: Patients receive TCRαβ+/CD19 B cell depleted donor stem cells IV over 30 minutes on day 0.
DONOR LYMPHOCYTE INFUSION (DLI): Patients receive CD19-CAR(Mem) T cells IV on day 14.
All patients also undergo collection of blood samples throughout the study. In addition, patients may undergo bone marrow aspiration/biopsy throughout the study.
After completion of study treatment, patients are followed up at months 1, 2, 3, 6, and 12, and then periodically for a total of 15 years.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorSwati Naik
