NCT06930651

A Phase I/II Study of CAR.70-Engineered IL15-Transduced Cord Blood-Derived NK Cells With TGF-beta Receptor 2 (TGFBR2) Knock Out in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Myeloid Malignancies

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical research study is to find the recommended safe dose of TGFBR2 KO CAR27/IL-15 NK cells that can be given to patients with relapsed/refractory disease. The safety and effectiveness of this treatment will also be studied.

Detailed description

This is a phase I/II, two-arm, open-label study. The study will have a phase I dose-escalation portion using a standard "BOIN" approach to determine the MTD of the CAR.70/IL15-transduced/TGFBR2KO CB-NK cells, followed by phase II expansions of 2 arms: 1.) patients with relapsed/refractory AML and 2.) patients with MDS/CMML after HMA failure. Up to 12 patients will be enrolled in the phase I portion of the study. Following determination of the recommended phase 2 dose (RP2D), 20 patients will be enrolled into the AML arm and 10 patients will be enrolled into the MDS/CMML arm (30 patients total in phase II). The regimen consists of lymphodepleting and priming chemotherapy with dexamethasone, decitabine, fludarabine and cyclophosphamide, followed by a one-time infusion of the CAR.70/IL15-transduced/TGFBR2KO CB-NK cells Primary Objectives: * Phase I: To determine the safety and optimal cell dose of TGFBR2 KO CAR27/IL-15 NK cells in patients with relapsed/refractory myeloid malignances * Phase II: To determine the response rates of TGFBR2 KO CAR27/IL-15 NK cells in patients with relapsed/refractory AML and in patients with MDS or CMML after HMA failure Secondary Objectives: * To determine the CR rate in each cohort * To determine the rate of flow cytometry MRD negativity (AML cohort only) * To assess duration of response, relapse-free survival (AML cohort only), and overall survival * To determine hematologic and non-hematologic toxicities Exploratory Objectives: * To assess impact of baseline cytomolecular features and CD70 expression on response * To quantify persistence of the infused CAR product * To conduct comprehensive immune reconstitution studies

Conditions

• Myeloid Malignancies

Interventions

Type	Name	Description
DRUG	Dexamethasone	Given Orally
DRUG	Cyclophosphamide	Given by IV
DRUG	Fludarabine	Given by IV
DRUG	Decitabine	Given by IV
BIOLOGICAL	TGFBR2 KO CAR27/IL-15 NK cells	Given by Infusion

Timeline

• Start date: 2025-09-03
• Primary completion: 2028-05-01
• Completion: 2030-05-01
• First posted: 2025-04-16
• Last updated: 2026-03-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study