Actively Recruiting
A Phase I/II Study of CAR.70-Engineered IL15-Transduced Cord Blood-Derived NK Cells with TGF-beta Receptor 2 Knock Out Combined with Chemotherapy for Relapsed/Refractory Myeloid Malignancies
Led by M.D. Anderson Cancer Center · Updated on 2026-05-06
42
Participants Needed
1
Research Sites
104 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying a new treatment for patients with relapsed or refractory myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML). This phase I/II open-label study aims to find the safest and most effective dose of CAR.70-engineered IL15-transduced cord blood-derived natural killer (NK) cells with TGF-beta receptor 2 knockout (TGFBR2 KO) combined with chemotherapy. The trial's goal is to assess safety, response rates, and several key outcomes related to disease control and patient survival. The treatment involves lymphodepleting and priming chemotherapy with dexamethasone, decitabine, fludarabine, and cyclophosphamide, followed by a one-time infusion of the modified NK cells. The study begins with a dose-escalation phase to determine the maximum tolerated dose (MTD) of these cells. After establishing the recommended phase 2 dose, two groups of patients will receive the treatment: one group with relapsed or refractory AML, and another with MDS or CMML after hypomethylating agent failure. Participants will undergo regular monitoring for safety and effectiveness, including assessments of response rates 30 days after infusion and safety follow-up for about one year. Researchers will also track remission rates, measurable residual disease, duration of response, relapse-free survival, overall survival, and both hematologic and non-hematologic side effects. Immune system recovery and the persistence of the infused cells will also be studied to better understand the treatment’s impact over time.
CONDITIONS
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 to 80 years
- Diagnosis of relapsed or refractory AML, treated secondary AML, intermediate to very-high risk MDS, or CMML
- Bone marrow blasts greater than 5% for MDS and CMML
- CD70 expression greater than 10% measured by immunohistochemistry or flow cytometry
- ECOG performance status 0 to 2
- Adequate liver, heart, kidney, and lung function as defined by study criteria
- Ability to understand and sign informed consent
- Willingness to comply with long-term follow-up
- Willingness to use effective contraception during and for 3 months after the study
You will not qualify if you...
- Active grade III to V heart failure
- Active serious infection not controlled by antibiotics
- Active central nervous system leukemia
- Known HIV infection unless well controlled on therapy
- Known active hepatitis B or C infection unless viral load is undetectable
- Prior or concurrent malignancies that interfere with study assessments unless approved
- Use of calcineurin inhibitors within 2 weeks before study
- Recent treatment with investigational antileukemic or chemotherapy agents within 7 days before lymphodepletion unless fully recovered or rapidly progressive disease
- Pregnant or breastfeeding women
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 2 weeks or until completion of chemotherapy and cell infusion
Participants receive lymphodepleting and priming chemotherapy with dexamethasone, decitabine, fludarabine, and cyclophosphamide, followed by a one-time infusion of CAR.70-engineered IL15-transduced cord blood-derived NK cells with TGF-beta receptor 2 knock out.
1 to 2 visits during chemotherapy and 1 infusion visit
Duration - Up to 1 year
Participants are monitored for safety, response rates, and adverse events for approximately one year after treatment.
Regular visits for safety and response assessments throughout the follow-up period
Trial Site Locations
Total: 1 location
1
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
N
Nicholas Short, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
2
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