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
M.D. Anderson Cancer Center
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.
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…
Eligibility
- Age range
- 18–80 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Diagnosis: Age 18-80 years with diagnosis of: 1. Relapsed or refractory AML or "treated secondary AML" * Patients with a mutation that is targetable with an FDA-approved targeted therapy should have received at least one on these agents. . "Treated secondary AML "includes patients with prior diagnosis of a myeloid neoplasm (e.g. MDS) who received hypomethylating agents for this disease and subsequently progressed to AML. These patients must have received all of the following: a hypomethylating agent + venetoclax and intensive chemotherapy (if a suitable candi…
Interventions
- DrugDexamethasone
Given Orally
- DrugCyclophosphamide
Given by IV
- DrugFludarabine
Given by IV
- DrugDecitabine
Given by IV
- BiologicalTGFBR2 KO CAR27/IL-15 NK cells
Given by Infusion
Location
- The University of Texas M. D. Anderson Cancer CenterHouston, Texas