Clinical Trials Directory

Trials / Withdrawn

WithdrawnNCT06572631

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

Phase 1b Expansion Study of Multi-Antigen Specific CD8+ T Cells After Decitabine-enhanced Lymphodepletion: An Adoptive Cellular Therapy for Patients With Relapsed or Refractory AML or MDS Following an Allogeneic Hematopoietic Cell Transplantation From Matched HLA Donors

Status
Withdrawn
Phase
Phase 1
Study type
Interventional
Enrollment
0 (actual)
Sponsor
City of Hope Medical Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. Characterize the safety of allogeneic CD8+ leukemia-associated antigens specific T cells NEXI-001 (NEXI-001) combined with decitabine. II. Determine the recommended phase 2 dose (RP2D) for NEXI-001 T cells combined with decitabine. SECONDARY OBJECTIVES: I. Investigate the preliminary anti-leukemic activity of NEXI-001 T cells combined with decitabine based on: Ia. Complete response (CR) rate; Ib. Overall response rate (ORR); Ic. Median duration of response; Id. 1-year overall survival (OS); Ie. 1-year progression-free survival (PFS). II. Cumulative incidence of acute graft-versus-host disease (aGVHD) of grades 2-4 and 3-4 at day 100 post first infusion of NEXI-001. III. Cumulative incidence of chronic graft-versus-host disease (cGVHD) of all grades at 1 year post first infusion of NEXI-001. IV. Characterize the T cells in the NEXI-001 product by immunophenotype and tumor antigen specificity. V. Characterize NEXI-001 T cells in peripheral blood (PB) and bone marrow (BM) by immunophenotype and tumor antigen specificity. VI. Expansion and persistence of NEXI-001 T cells in PB and BM. EXPLORATORY OBJECTIVES: I. Evaluate the effect of the following factors on the safety and efficacy of NEXI-001 T cells combined with decitabine: Ia. NEXI-001 T-cell immunophenotype; Ib. Persistence of NEXI-001 T cells in PB and BM; Ic. Blood levels of the antigen-specific NEXI-001 T cells; Id. Biomarkers of activation, proliferation, and exhaustion of T cells; Ie. The expression of tumor associated antigen (TAAs) and checkpoint molecules on AML blasts. OUTLINE: This is a dose-escalation study of decitabine in combination with NEXI-001, fludarabine and cyclophosphamide. DONOR: Donors undergo leukapheresis on study. PATIENTS: Patients may receive bridging therapy per standard of care ≥ 14 days prior to the start of cycle 1. Patients receive decitabine intravenously (IV) over 1 hour once per day (QD) on day -3, -5 or -10 to day -1, lymphodepletion chemotherapy with fludarabine IV over 30 minutes QD and cyclophosphamide IV over 60 minutes QD on day -5 to -3 and then receive NEXI-001 IV over 30 minutes QD on days 1, 8 and 15 of cycle 1. Cycles repeat every 33 or 38 days in the absence of disease progression or unacceptable toxicity. If NEXI-001 cells remain and treatment criteria are met, patients may receive and additional cycle of decitabine IV over 1 hour QD on day -5 to -1 and NEXI-001 IV QD on days 1, 8 and 15 in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) during screening, bone marrow aspirate and/or bone marrow biopsy, positron emission tomography (PET)/computed tomography (CT) scan or magnetic resonance imaging (MRI) and blood sample collection throughout the study. After completion of study treatment, patients are followed up within 30 days and every 3 months for up to 1 year.

Conditions

Interventions

TypeNameDescription
BIOLOGICALAllogeneic CD8+ Leukemia-associated Antigens Specific T Cells NEXI-001Given IV
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREBone Marrow AspirationUndergo bone marrow aspiration
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy
PROCEDUREComputed TomographyUndergo PET/CT
DRUGCyclophosphamideGiven IV
DRUGDecitabineGiven IV
PROCEDUREEchocardiographyUndergo ECHO
DRUGFludarabineGiven IV
PROCEDURELeukapheresisUndergo leukapheresis
PROCEDUREMagnetic Resonance ImagingUndergo MRI
PROCEDUREPositron Emission TomographyUndergo PET/CT

Timeline

Start date
2025-06-07
Primary completion
2026-12-12
Completion
2026-12-12
First posted
2024-08-27
Last updated
2025-05-25

Regulatory

Source: ClinicalTrials.gov record NCT06572631. Inclusion in this directory is not an endorsement.