City of Hope Medical Center
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.
PRIMARY OBJECTIVES: I. Describe toxicities attributable to total marrow and lymphoid irradiation (TMLI) by dose level in patients with high-risk acute leukemias or MDS, in the context of partially engineered T-regulatory cell donor graft TRGFT-201 (Orca-T) from a matched or haploidentical donor. II. Determine the recommended phase II dose (RP2D) of TMLI with an Orca-T for allogeneic hematopoietic cell transplantation (HCT). SECONDARY OBJECTIVES: I. Determine incidence of acute and late HCT-related immune complications (infections, etc.) at 100 days and 1 year. II. To evaluate the safety o…
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 catego…
Undergo blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo DECT/MRI scan
Undergo echocardiography
Given IV
Undergo DECT/MRI scan
Given IV
Undergo MUGA scan
Given IV
Given tacrolimus
Given IV
Undergo TMLI