A Single Center, Non-Randomized, Phase 1b Study of Orca-T Following Escalated Dose of Total Marrow and Lymphoid Irradiation in Patients With Acute Leukemias and MDS
City of Hope Medical Center
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.
Description
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…
Eligibility
- Age range
- 60+ years
- Sex
- All
- Healthy volunteers
- Yes
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…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- ProcedureDual-Energy Computed Tomography
Undergo DECT/MRI scan
- ProcedureEchocardiography
Undergo echocardiography
- DrugFludarabine
Given IV
- ProcedureMagnetic Resonance Imaging
Location
- City of Hope Medical CenterDuarte, California