Phase I Trial of Modified T Cells Targeting Specific Neoantigens in Adults with Blood Cancers Including Leukemia and Myelodysplastic Syndrome

What this Trial Is About

Researchers are studying treatments for difficult-to-treat blood cancers, including acute myeloid leukemia, myelodysplastic syndrome, and other hematologic malignancies, especially those with mutations in the TP53 or RAS genes. These mutations create unique substances called neoepitopes that can be targeted by modified immune cells. This phase I trial aims to test the safety of giving participants genetically altered T cells that specifically target these neoepitopes alongside chemotherapy and a drug called aldesleukin. Participants will undergo blood collection to separate and grow their T cells, which will be genetically modified to recognize their cancers neoepitopes. Before receiving these cells, they will have a conditioning chemotherapy regimen with cyclophosphamide and fludarabine for three days. The modified T cells are then infused into a vein, followed by aldesleukin given intravenously. Participants stay hospitalized for at least seven days after the infusion to monitor for side effects. Throughout the first year after treatment, participants will have eight follow-up visits for monitoring and cancer assessments, followed by six additional visits over the next four years. Long-term monitoring will continue for up to ten years to assess safety and treatment effects. The study will measure safety from the start of chemotherapy through five years post-infusion and assess overall response and feasibility of treatment manufacturing.

Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies