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

NCT06930651 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-1967NCI-2025-02697
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloid Malignancies

Outcome Measures

Primary Outcomes (3)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

• Response rates (AML cohort)

  Rate of complete remission (CR) + CR with incomplete hematologic recovery (CRi) + CR with CR with partial hematologic recovery (CRh)

  30 days from CAR infusion

• Response rates (MDS/CMML) cohort

  Rate of CR + partial remission (PR) + CR with limited count recovery (CRL), CRh, hematologic improvement (HI) for MDS; rate of CR + PR + marrow CR (mCR) + clinical benefit (CB) for CMML

  30 days from CAR infusion

Secondary Outcomes (6)

• CR rate

  30 days from CAR infusion

• Measurable residual disease (MRD) negativity (AML cohort)

  30 days from CAR infusion

• Duration of response

  Through study completion; an average of 1 year

• Relapse-free survival

  Through study completion; an average of 1 year

• Overall survival

  Through study completion; an average of 1 year

Study Arms (2)

Phase 1: Dose Escalation with CAR.70

EXPERIMENTAL

Participants will receive lymphodepleting and primary chemotherapy, followed by a one-time infusion of TGFR KO-CAR27/IL-15 NK cells. Dose of the cells will be a different dose until a maximum tolerated dose is found.

Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Decitabine; Biological: TGFBR2 KO CAR27/IL-15 NK cells

Phase 2A: Dose Expansion with CAR.70 for AML Patients

EXPERIMENTAL

Participants will receive lymphodepleting and primary chemotherapy, followed by a one-time infusion of TGFR KO-CAR27/IL-15 NK cells using the maximum tolerated dose found in escalation

Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Decitabine; Biological: TGFBR2 KO CAR27/IL-15 NK cells

Interventions

Dexamethasone DRUG

Given Orally

Phase 1: Dose Escalation with CAR.70; Phase 2A: Dose Expansion with CAR.70 for AML Patients

Cyclophosphamide DRUG

Given by IV

Phase 1: Dose Escalation with CAR.70; Phase 2A: Dose Expansion with CAR.70 for AML Patients

TGFBR2 KO CAR27/IL-15 NK cells BIOLOGICAL

Given by Infusion

Phase 1: Dose Escalation with CAR.70; Phase 2A: Dose Expansion with CAR.70 for AML Patients

Fludarabine DRUG

Given by IV

Phase 1: Dose Escalation with CAR.70; Phase 2A: Dose Expansion with CAR.70 for AML Patients

Decitabine DRUG

Given by IV

Phase 1: Dose Escalation with CAR.70; Phase 2A: Dose Expansion with CAR.70 for AML Patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis: Age 18-80 years with diagnosis of:
• 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 candidate for intensive therapy). These patients may be enrolled at the time of AML diagnosis if they have already received all of the treatments above for their antecedent myeloid neoplasm.
• MDS that is intermediate, high-risk or very-high risk by the Revised International Prognostic Scoring System (R-IPSS)
• Bone marrow blasts must be \>5%.
• The disease must have either 1.) not have responded to at least 4 cycles of a hypomethylating agent or 2.) progressed or relapsed, regardless of the number of cycles received
• CMML-1 or CMML-2
• Bone marrow blasts must be \>5%.
• The disease must have either 1.) not have responded to at least 4 cycles of a hypomethylating agent or 2.) progressed or relapsed, regardless of the number of cycles received
• CD70 expression \>10% measured by immunohistochemistry or multiparameter flow cytometry
• Performance status \</=2 (ECOG Scale)
• Adequate liver, cardiac, renal and pulmonary function as defined by the following criteria:
• Total serum bilirubin \</=2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \</=3 x ULN, unless due to the underlying leukemia approved by the PI
• Serum creatinine \</=2x ULN or creatinine clearance \>/=30 mL/min

You may not qualify if:

• Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
• Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
• Active central nervous system leukemia
• Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
• Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection Note: Patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
• Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
• Use of calcineurin inhibitors (e.g. tacrolimus) within the past 2 weeks
• Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before lymphodepletion, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator.
• i. Prior recent treatment with corticosteroids, hydroxyurea, and/or cytarabine (up to 2 g/m2 given for cytoreduction within the preceding 7 days) is permitted up until 1 day prior to lymphodepletion.
• Patients may continue on non-investigational targeted therapies up until 3 days prior to lymphodepletion.
• Pregnant or breastfeeding women will not be eligible

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

Dexamethasone; Cyclophosphamide; fludarabine; Decitabine

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Nicholas Short, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas Short, MD

CONTACT

(713) 563-4485; nshort@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 16, 2025
• Study Start: September 3, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)