Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome
Trial Parameters
Brief Summary
This phase I trial tests the side effects and best dose of total marrow lymphoid irradiation along with chemotherapy, with fludarabine and melphalan, with or without thiotepa, in combination with Orca-T cells for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS). Total marrow and lymphoid irradiation is a targeted form of total body irradiation that uses intensity-modulated radiation therapy to target marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize the radiation therapeutic effect. Giving chemotherapy with medications such as thiotepa, fludarabine, and melphalan before a treatment with stem cells helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Orca-T cells take cells from a donor and remove some of the T cells and replace them with partially engineered T cells in order to induce better tolerance in patients. Giving total marrow and lymphoid irradiation and chemotherapy followed by Orca -T cells may be an effective treatment for patients with AML, ALL or MDS.
Eligibility Criteria
Inclusion Criteria: * Documented informed consent of the participant * Agreement to allow the use of archival tissue from diagnostic bone marrow biopsies * If unavailable, exceptions may be granted with study primary investigator (PI) approval * Age: 60-75 years * Karnofsky performance status ≥ 70 * Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories: * Acute myelogenous leukemia: * Patients with de novo or secondary disease in CR1 or more with European LeukemiaNet (ELN) intermediate or adverse risk category, or * Patients with active disease * Morphologically; or * Minimal residual disease (MRD) + (flow cytometry of ≥ 0.1%, next generation sequencing \[NGS\] or cytogenetics) * Acute lymphoblastic leukemia (ALL): * Patients with de novo or secondary disease according to National Comprehensive Cancer Network (NCCN) guidelines for ALL hypoploidy (\< 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2