Disease: Relapsed or Refractory Acute Lymphocytic Leukemia, ALL, (NCT06481735)
Disease info:
Leukaemia is cancer of the white blood cells which are responsible for fighting infection. In leukaemia, the bone marrow produces abnormal levels of white blood cells. B-cell acute lymphoblastic leukaemia (B-ALL) is an aggressive (fast-growing) type of leukaemia in which too many B-cell lymphoblasts (immature white blood cells) are found in the bone marrow and blood. It is the most common type of ALL. Also called B-cell acute lymphocytic leukaemia and precursor B-lymphoblastic leukaemia.
Relapsed refers to when a patient has received active treatment, went off treatment and then the disease came back, whereas refractory refers to disease that is progressing despite active treatment.
Frequency:
ALL accounts for less than 1% of all cancers in the U.S., with around 6,540 new cases estimated in the U.S. in 2023. ALL is the most common type of cancer found in children, though it can affect adults too.
Official title:
A Phase 1/2 Single-center Study Evaluating the Safety and Efficacy of TCR Reserved and Power3 Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in Adults With Refractory/Relapsed B-cell Acute Lymphoblastic Leukaemia
In this study, investigators will disable the Power3 gene of T cells from healthy donors to prepare CAR T cells. This approach harnesses the tonic signaling of CAR T cells, resulting in enhanced persistence and improved response to treatment. The purpose of this study is to evaluate the safety and efficacy of allogeneic Power3 knock-out CD19 CAR-T in B-cell acute lymphoblastic leukaemia (B-ALL).
Phase 1 (dose escalation)
In phase 1, 6-18 subjects will be enrolled. Subjects will receive 3 doses of allogeneic Power3 knock-out CD19 CAR-T cell therapy ( 1 × 10^6 cells/kg、3 × 10^6 cells/kg、6 × 10^6 cells/kg) increases from low dose to high dose according to the "3 + 3" principle:
Three (3) subjects are enrolled in a cohort corresponding to a dose level. If 1 subject in a cohort of 3 subjects experiences a dose-limiting toxicity (DLT), 3 additional subjects will be enrolled at the current dose level. For safety purposes, the administration of allogeneic Power3 knock-out CD19 CAR-T will be staggered by 28 days between the first two subjects in each cohort. And for each of the remaining cohorts, the administration of allogeneic Power3 knock-out CD19 CAR-T will be staggered by 28 days before enter into the next cohort.
Phase 2 (expansion cohort)
In phase 2, 10 to 12 subjects will be enrolled and receive cell infusion at dose of recommended phase 2 dose (RP2D), which will be determined based on the maximum tolerated dose (MTD), occurrence of DLT, the obtained efficacy results, pharmacokinetics/pharmacodynamics and other data according to the phase 1.
Objectives
The primary objectives of the phase 1 were to evaluate the tolerability and safety of allogeneic Power3 knock-out CD19 CAR-T in patients with refractory/relapsed (r/r) B-ALL, and determine RP2D. The primary purpose of the phase 2 study was to evaluate the efficacy of allogeneic Power3 knock-out CD19 CAR-T in the above population.
