NCT06383572

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

To find a recommended dose of PRAME-TCR-NK cells that can be given to patients with AML or MDS.

Detailed description

PRIMARY OBJECTIVE: I. To assess dose-limiting toxicity (DLT) and determine the safety, day 30 response rate, day 180 treatment failure rate (defined as disease progression or death) and optimal cell dose of T cell receptor (TCR) modified cord blood-natural killer (CB-NK) cells (TCR-NK) targeting PRAME in patients with relapsed/refractory myeloid malignances, for each of the following diseases; AML, and MDS/CMML. The day 30 response rate and day 180 treatment failure rate will be estimated, and the estimates will be used to identify an optimal dose of PRAME-TCR-NK cells. SECONDARY OBJECTIVES: I. To assess the preliminary efficacy of PRAME-TCR-NK cells (day+ 30 complete and partial response rates; day 180 progression-free survival rate) in patients with relapsed/refractory AML and MDS. II. To quantify persistence of infused allogeneic donor PRAME-TCR CB-derived NK cells in the recipient as an integrated evaluation. III. To conduct comprehensive immune reconstitution studies. IV. To obtain preliminary data on quality of life and patient experience (Patient Reported Outcomes Measurement Information Systems \[PROMIS\]-29 quality of life questionnaire score). OUTLINE: This is a phase I dose-escalation study of PRAME-TCR-NK followed by a phase II study. Patients receive dexamethasone orally (PO) on days -10, -9, -8, -7, and -6, decitabine intravenously (IV) over 1 hour on days -6, -5, and -4, fludarabine IV over 30 minutes and cyclophosphamide IV over 60 minutes on days -5, -4, and -3 and PRAME-TCR-NK cells IV over 2-20 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and computed tomography (CT) or chest x-ray pre-treatment and bone marrow aspiration and biopsy, and blood sample collection throughout the study. After completion of study treatment, patients are followed up for 24 months then for at least 15 years per protocol PA17-0483. Sponsor: M D Anderson Cancer Center Lead Organization: M D Anderson Cancer Center Principal Investigator: Ramdial, Jeremy Responsible Party: Sponsor Overall Official: Ramdial, Jeremy (Principal Investigator), M D Anderson Cancer Center

Conditions

• Lymphodepleting Chemotherapy
• Myeloid Malignancies

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given by IV
DRUG	Fludarabine phosphate	Given by IV
DRUG	Decitabine	Given by IV
DRUG	Dexamethasone	Given by mouth

Timeline

• Start date: 2024-06-26
• Primary completion: 2027-04-01
• Completion: 2029-04-01
• First posted: 2024-04-25
• Last updated: 2025-12-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study