Multi-antigen Specific CD8+ T Cells With Decitabine and Lymphodepleting Chemotherapy for the Treatment of Patients With Relapsed or Refractory AML or MDS Following an Allogeneic Hematopoietic Cell Transplantation From a Matched Donor
NCT Number: NCT06572631
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Recurrent Acute Myeloid Leukemia|Recurrent Myelodysplastic Syndrome|Refractory Acute Myeloid Leukemia|Refractory Myelodysplastic Syndrome
Interventions: BIOLOGICAL: Allogeneic CD8+ Leukemia-associated Antigens Specific T Cells NEXI-001|PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|PROCEDURE: Bone Marrow Biopsy|PROCEDURE: Computed Tomography|DRUG: Cyclophosphamide|DRUG: Decitabine|PROCEDURE: Echocardiography|DRUG: Fludarabine|PROCEDURE: Leukapheresis|PROCEDURE: Magnetic Resonance Imaging|PROCEDURE: Positron Emission Tomography
Sponsor: City of Hope Medical Center
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 31
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-07
Completion Date: 2026-12-12
Locations: City of Hope Medical Center, Duarte, California, 91010, United States

Summary:
This phase I trial tests the safety, side effects and best dose of NEXI-001 when given with decitabine and lymphodepleting chemotherapy in treating patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory) following an allogeneic hematopoietic cell transplantation from a matched donor. NEXI-001 is a type of chimeric antigen receptor T cell therapy in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Lymphodepleting chemotherapy, with fludarabine and cyclophosphamide, helps kill cancer cells in the body and helps prepare the body for the new CAR-T cells. Giving NEXI-001 with decitabine and lymphodepleting chemotherapy may be safe and tolerable in treating patients with relapsed or refractory AML or MDS following an allogeneic hematopoietic cell transplantation from a matched donor.

Primary Outcome Measures: Incidence of adverse events (AEs), AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, with the following exceptions: cytokine Release Syndrome will be graded according to the consensus criteria published by the American Society for Transplantation and Cellular Therapy, Immune effector Cell-Associated Neurotoxicity Syndrome, acute graft versus host disease (GVHD) grading according to Magic Consortium criteria and chronic GVHD grading according to National Health Institute Consensus criteria., Up to 1.5 years|Dose limiting toxicity, Defined as grade 3 or higher non-hematological AE excluding toxicities unequivocally related to underlying disease, intercurrent illness or alternative etiology, and with the following exceptions: grade 3 or higher cytokine release syndrome/neurotoxicity that responds to appropriate medical intervention within 72 hours before improving to \< grade 2 and grade 3-4 GVHD if responsive to therapy within 14-21 days., Up to completion of cycle 1
Secondary Outcome Measures: Overall response, By the 2022 European Leukemia Net criteria for acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Will be analyzed using the Kaplan-Meier method., Up to 1.5 years|Complete response, By morphologic, multiparametric flow cytometry, and real time quantitative polymerase chain reaction criteria. Will be analyzed using the Kaplan-Meier method., Up to 1.5 years|Duration of response, Will be analyzed using the Kaplan-Meier method., From the starting date of response to the date of disease progression, up to 1.5 years|Progression free survival, Will be analyzed using the Kaplan-Meier method., From starting study therapy to the first observation of disease progression or date of death, whichever comes first, up to 1.5 years|Overall survival, Will be analyzed using the Kaplan-Meier method., From starting study therapy to the date of death, up to 1.5 years|Determine the immunophenotype of NEXI-001 T cells, In peripheral blood (PB) and bone marrow (BM) by flow cytometry techniques., Up to 1.5 years|Incidence of acute GVHD, Of grades 2-4 and 3-4 (grading according to Magic Consortium criteria). Will be calculated using death and disease progression as competing risks., Up to 1.5 years|Incidence of chronic GVHD, Of all grades (grading according to Lee et al. 2017). Will be calculated using death and disease progression as competing risks., Up to 1.5 years|Persistence/antigen specificity of NEXI-001 T cells, In PB and BM by multimer-based staining over time., Up to 1.5 years