Seattle Children's Hospital
This is a phase I, open-label, non-randomized clinical trial that will enroll pediatric and adult research participants with CLEC2A+ acute myeloid leukemia (AML) that does not go away with treatment (is refractory) or comes back after treatment (is recurrent). The goal is to evaluate the safety, feasibility, and efficacy of administering T cell products (modified immune cells) derived from the research participant's blood that have been genetically modified to express chimeric antigen receptor (CAR) targeting SC-CAR.CLEC2Av1. The main questions it seeks to answer are: * How safe is the T cell product infusion (modified immune cells)? * How feasible is it to manufacture the cell products? Participants will first receive treatments to prepare their body (bridging therapy and lymphodepletion). On Day 0, they receive a single infusion of CLEC2A CAR T cells, which are modified immune cells designed to target and fight cancer. Researchers will evaluate the safety and side effects of the treatment, check how well the CAR T cells survive and multiply in the body over time (using blood, bone marrow, and cerebrospinal fluid samples), and assess how well the treatment fights the AML. Bone marrow tests are performed on Day 28 to check the response.
Inclusion Criteria: * Subject age ≤ 70 years * Weight ≥ 7 kilograms * AML that expresses CLEC2A by flow cytometry as assessed by Hematologics, Inc. Laboratory and meets one of the below definitions: 1. for subjects who have previously received an allogeneic HCT, any evidence of AML post HCT detectable by flow cytometry. 2. first or greater relapse of AML. 3. refractory AML, defined as ≥ 0.1% leukemic cells determined by flow cytometry or \>1% on biopsy after 2 cycles of chemotherapy. * Able to tolerate apheresis * Life expectancy ≥ 8 weeks * Has an appropriate stem cell donor source id…
Subjects will receive a single dose of CLEC2A CAR T cells. CD4+ and CD8+ T cell subsets will be isolated from an apheresis product obtained from the research participant. The isolated cells will be stimulated with a anti-CD3/28 activation reagent beads and transduced with a self-inactivating (SIN) lentiviral vector that directs the expression of the CLEC2A CAR.