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

NCT06572631 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 23606NCI-2024-06709P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Recurrent Acute Myeloid Leukemia; Recurrent Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Overall response

  Up to 1.5 years

• Complete response

  Up to 1.5 years

• Duration of response

  From the starting date of response to the date of disease progression, up to 1.5 years

• Progression free survival

  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

  From starting study therapy to the date of death, up to 1.5 years

Study Arms (1)

Treatment (NEXI-001, decitabine, chemotherapy)

EXPERIMENTAL

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 IV over 1 hour 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 ECHO during screening, bone marrow aspirate and/or bone marrow biopsy, PET/ CT scan or MRI and blood sample collection throughout the study.

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

Interventions

Allogeneic CD8+ Leukemia-associated Antigens Specific T Cells NEXI-001 BIOLOGICAL

Given IV

Also known as: NEXI 001, NEXI-001, NEXI001

Treatment (NEXI-001, decitabine, chemotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (NEXI-001, decitabine, chemotherapy)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (NEXI-001, decitabine, chemotherapy)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (NEXI-001, decitabine, chemotherapy)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (NEXI-001, decitabine, chemotherapy)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (NEXI-001, decitabine, chemotherapy)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (NEXI-001, decitabine, chemotherapy)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (NEXI-001, decitabine, chemotherapy)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (NEXI-001, decitabine, chemotherapy)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (NEXI-001, decitabine, chemotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (NEXI-001, decitabine, chemotherapy)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (NEXI-001, decitabine, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PARTICIPANT: Documented informed consent of the participant and/or legally authorized representative and documented informed consent of the donor
• PARTICIPANT: Agreement to allow the use of archival tissue from diagnostic tumor biopsies (if unavailable, exceptions may be granted with study principal investigator \[PI\] approval)
• PARTICIPANT: Age: ≥ 18 years
• PARTICIPANT: Eastern Cooperative Oncology Group (ECOG) ≤ 1 or Karnofsky performance score (KPS) ≥ 70
• PARTICIPANT: Confirmed diagnosis of AML/MDS that has relapsed after or is refractory to an allogeneic hematopoietic cell transplantation (HCT) from a matched donor.
• Refractory - failure to achieve a complete response minimal residual disease (CRMRD) (-) by multicolor flow cytometry (MFC) or reverse transcription polymerase chain reaction (RT qPCR)
• Relapse - detection of clonal abnormal myeloid blasts by morphology (morphologic relapse) or by MFC, or RT-qPCR analysis (MRD\[+\] relapse) after achieving a CRMRD(-) induced by an allogeneic HCT or maintained by allogeneic HCT administered as consolidation therapy.
• Note: Patients who meet the protocol definition of relapse/refractory (r/r) AML/MDS at screening and subsequently achieve a CRMRD(-) response status following protocol-specified bridging therapy will remain eligible to continue participation in this study
• PARTICIPANT: At least 100 days post allogeneic HCT
• PARTICIPANT: Donor match at 8 out of 8 loci for human leucocyte antigen (HLA) -A, -B, -C, and -DRB1 (each typed at high resolution by deoxyribonucleic acid \[DNA\]-based methods)
• PARTICIPANT: Expression of HLA-A\*0201 as determined by high resolution sequence-based typing methods
• PARTICIPANT: Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (to be performed within 28 days of consenting)
• PARTICIPANT: Aspartate aminotransferase (AST) ≤ 2.5 x ULN (to be performed within 28 days of consenting)
• PARTICIPANT: Alanine aminotransferase (ALT) ≤ 2.5 x ULN (to be performed within 28 days of consenting)
• PARTICIPANT: Serum creatinine \< 1.5 mg/dL or creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (to be performed within 28 days of consenting)

You may not qualify if:

• PARTICIPANT: Patients who have had 2 prior allogeneic (allo) HCTs
• PARTICIPANT: Patients who have received more than 3 anti-leukemic treatments regimens since their allo HCT
• PARTICIPANT: Vaccination with a live virus within six months prior to study treatment.
• Inactivated influenza vaccination is allowed
• PARTICIPANT: Active acute or chronic GVHD
• PARTICIPANT: Known hypersensitivity to any component of the NEXI-001 T-cell product or fludarabine, cyclophosphamide, decitabine, or tocilizumab
• PARTICIPANT: Clinically significant uncontrolled illness
• PARTICIPANT: A second primary malignancy that has not been in remission for \> 2 years. Exceptions include the following resected lesions:
• Non-melanoma skin cancer.
• Carcinoma in situ.
• Squamous intraepithelial lesions on Pap smear.
• Localized prostate cancer (Gleason score \< 6).
• Melanoma in situ
• PARTICIPANT: Females only: Pregnant or breastfeeding
• PARTICIPANT: Clinically significant cardiovascular disease:

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Specimen Handling; Biopsy; Cyclophosphamide; Decitabine; Injections; fludarabine; Leukapheresis; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Cytapheresis; Biological Therapy; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Monzr M Al Malki, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 27, 2024
• Study Start: June 7, 2025
• Primary Completion (Estimated): December 12, 2026
• Study Completion (Estimated): December 12, 2026
• Last Updated: May 25, 2025

Record last verified: 2025-05