Ignite Creation Date:
2025-12-24 @ 11:56 PM
Ignite Modification Date:
2026-01-02 @ 12:33 PM
Study NCT ID:
NCT06930651
Status:
RECRUITING
Last Update Posted:
2025-10-10
First Post:
2025-04-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
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
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2025-02697 | OTHER | NCI-CTRP Clinical Trials Registry | View |