Phase III Study of CAR.70-Engineered IL15-Transduced Cord Blood NK Cells with TGFBR2 Knock Out and Chemotherapy for Relapsed or Refractory Myeloid Malignancies

What this Trial Is About

Researchers are studying a new treatment for patients with relapsed or refractory myeloid malignancies, including acute myeloid leukemia AML, myelodysplastic syndromes MDS, and chronic myelomonocytic leukemia CMML. This phase III open-label study aims to find the safest and most effective dose of CAR.70-engineered IL15-transduced cord blood-derived natural killer NK cells with TGF-beta receptor 2 knockout TGFBR2 KO combined with chemotherapy. The trials goal is to assess safety, response rates, and several key outcomes related to disease control and patient survival. The treatment involves lymphodepleting and priming chemotherapy with dexamethasone, decitabine, fludarabine, and cyclophosphamide, followed by a one-time infusion of the modified NK cells. The study begins with a dose-escalation phase to determine the maximum tolerated dose MTD of these cells. After establishing the recommended phase 2 dose, two groups of patients will receive the treatment one group with relapsed or refractory AML, and another with MDS or CMML after hypomethylating agent failure. Participants will undergo regular monitoring for safety and effectiveness, including assessments of response rates 30 days after infusion and safety follow-up for about one year. Researchers will also track remission rates, measurable residual disease, duration of response, relapse-free survival, overall survival, and both hematologic and non-hematologic side effects. Immune system recovery and the persistence of the infused cells will also be studied to better understand the treatments impact over time.

A Phase I/II Study of CAR.70-Engineered IL15-Transduced Cord Blood-Derived NK Cells With TGF-beta Receptor 2 (TGFBR2) Knock Out in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Myeloid Malignancies