This phase I trial studies the safety, side effects, and best dose of genetically engineered cells called 19(T2)28z1XX TRAC-chimeric antigen receptor (CAR) T-cells in treating patients with CD19-positive B-cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). 19(T2)28z1XX TRAC-CAR T cells are made in the laboratory using collected white blood cells (T-cells). T cells are important protective cells of the immune system. The T cells have been genetically modified (changes are made to the DNA or genes) to help them identify, fight, or kill cancer cells. A virus (retrovirus) and a new technology called CRISPR/Cas9 are used to introduce a gene to a specific location (called TRAC) that creates a protein (called a chimeric antigen receptor or CAR) on the surface of T cells to identify and kill cancer cells. The retrovirus then becomes inactive. The 19(T2)28z1XX TRAC-CAR T cells can recognize a protein called CD19, which is found on the surface of B-cell cancer cells, and destroy those cells.
Additional locations may be listed on ClinicalTrials.gov for NCT05757700.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To estimate the safety and tolerability of TRAC locus integrated anti-CD19 19(T2)28z1xx CAR-T Cells (19(T2)28z1XX TRAC-CAR T cells) in the treatment of relapsed/refractory (R/R) large B-cell lymphoma.
II. To identify the recommended phase II dose (RP2D) of 19(T2)28z1XX TRAC-CAR T cells.
SECONDARY OBJECTIVES:
I. To estimate the efficacy of 19(T2)28z1XX TRAC-CAR T cells in patients as measured by the overall response rate (ORR), complete response (CR) rate, and progression-free survival (PFS).
II. To estimate the in vivo expansion and persistence of 19(T2)28z1XX TRAC-CAR T cells in patients.
III. To assess the immunogenicity of 19(T2)28z1XX TRAC-CAR T cells.
EXPLORATORY OBJECTIVES:
I. To assess the development and duration of B cell aplasia in treated patients.
II. To assess the levels of minimal residual disease (MRD) following modified T cell infusions.
III. To assess the T cell phenotype of persisting 19(T2)28z1XX TRAC-CAR T cells.
IV. To study the proinflammatory and immune-suppressive cytokines across the study time points.
OUTLINE: This is a phase I, dose-escalation study of 19(T2)28z1XX TRAC-CAR T cells followed by a dose-expansion study.
Patients undergo leukapheresis during screening. Patients receive conditioning chemotherapy consisting of cyclophosphamide intravenously (IV) and fludarabine IV on days -5 to -3, or bendamustine IV on days -4 and -3. Patients then receive 19(T2)28z1XX TRAC-CAR T cells IV 2-7 days after completion of conditioning chemotherapy. Patients also undergo multi-gated acquisition (MUGA) or echocardiography (ECHO) during screening, and computed tomography (CT) or positron emission tomography (PET) scan during screening, at 4, 12, and 24 weeks, and then as clinically indicated thereafter. Patients also undergo a lymph node or tumor biopsy during screening and 4 weeks after CAR T cell infusion, bone marrow aspirate and biopsy during screening, week 12, and as clinically indicated thereafter, and collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at weeks 1-4, at 2-6, 9, and 12 months, and then yearly for up to 15 years total.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorJae Park
