NCT07444632

Brief Summary

This is a phase 1 basket trial of TGFBR2 KO CAR27/IL-15 NK cells after lymphodepleting chemotherapy for patients with R/R B-NHL, HL, T-NHL or B-ALL.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
74mo left

Started Aug 2026

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 26, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 3, 2026

Completed
6 months until next milestone

Study Start

First participant enrolled

August 31, 2026

Expected
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2030

2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2032

Last Updated

May 8, 2026

Status Verified

May 1, 2026

Enrollment Period

4.1 years

First QC Date

February 26, 2026

Last Update Submit

May 5, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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

Study Arms (2)

Cycle 1: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK Cells

EXPERIMENTAL

Each treatment cycle will consist of lymphodepleting chemotherapy, followed by infusion of the TGFBR2 KO CAR27/IL-15 NK cells. Participants will be admitted to the inpatient service on day -6.

Drug: FludarabineDrug: TGFBR2 KO CAR27/IL-15 NK cellsDrug: Cyclophosphamide

Cycle 2: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK Cells

EXPERIMENTAL

Each treatment cycle will consist of lymphodepleting chemotherapy, followed by infusion of the TGFBR2 KO CAR27/IL-15 NK cells. Participants will be admitted to the inpatient service on day -6.

Drug: FludarabineDrug: TGFBR2 KO CAR27/IL-15 NK cellsDrug: Cyclophosphamide

Interventions

Given by IV

Also known as: Fludara
Cycle 1: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK CellsCycle 2: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK Cells

Given by IV

Cycle 1: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK CellsCycle 2: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK Cells

Given by IV

Also known as: Cytoxan
Cycle 1: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK CellsCycle 2: Treatment with Fludarabine and Cyclophosphamide + TGFBR2 KO CAR27/IL-15 NK Cells

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age.
  • Diagnosis of relapsed B-NHL, HL, T-NHL, or B-ALL in refractory relapse, defined as:
  • B-NHL: Failure of \>/= 1 salvage line and failure of or ineligibility for CAR-T.
  • HL and T-NHL: Failure of \>/= 1 salvage line or prior SCT.
  • ALL: Active disease (\>5% of blasts or positive MRD at a level of \>0.1% measured by multiparameter flow cytometry) after ≥ 2 two lines of therapy. Patients with B-ALL must have either failed of or be ineligible for CAR-T cell therapy. Patients who have mutations for which there are FDA approved targeted therapies (i.e., BCR-ABL) must also have received at least one of such agents.
  • Expression of CD70 in the pre-enrollment sample \>/= 20% measured by immunohistochemistry or flow cytometry.
  • Measurable disease, defined by \>/= 1 histologically confirmed hypermetabolic lesion on PET/CT scan.
  • ECOG PS ≤ 2 (Karnofsky ≥60%).
  • Adequate blood counts (WBC \>/= 2K, HGB \>/= 8 g/dL, platelets \>/= 50K).
  • Creatinine clearance ≥ 30 ml/min.
  • ALT and/or AST ≤ 3 x ULN, and bilirubin and ALP ≤ 2 x ULN.
  • FEV1, FVC and DLCOc ≥ 50%.
  • LVEF ≥ 40%, without active arrythmias.
  • If female of child-bearing potential, she must not be pregnant or breastfeeding and required to have a negative urine or serum pregnancy test prior to enrollment.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • +14 more criteria

You may not qualify if:

  • Lymphoma or ALL in CR with no measurable sites of disease.
  • Major surgery \<4 weeks prior to first dose of study drug.
  • Any other severe or uncontrolled disease or condition which mightincrease the risk associated with study participation.
  • Any other malignancy known to be active, with the exception of treated cervical intraepithelial neoplasia and non-melanoma skincancer.
  • Grade \>/= 3 non-hematologic toxicity from prior therapy that has notimproved to grade \</= 2.
  • Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/=10,000 copies/mL, or \>/=2,000 IU/mL), or hepatitis C (detectable viral load by HCV RNA PCR).
  • Active infection requiring parenteral antibiotics.
  • HIV infection.
  • Treatment within prior 2 weeks with any anti-cancer agent,investigational or approved.
  • Active CNS involvement (untreatedparenchymal brain metastasis or positive cytology of cerebrospinal fluid).
  • Life expectancy \</= 6 months.
  • Active and uncontrolled neurological disorder.
  • Patients receiving systemic steroid therapy at time of enrollment (physiological replacement doses are allowed) or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment.
  • Patients receiving immunosuppressive therapy.
  • Patients who are receiving any other investigational agents.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

Hodgkin Disease

Interventions

fludarabinefludarabine phosphateCyclophosphamide

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Yago Nieto, MD, PHD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yago Nieto, MD, PHD

CONTACT

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

February 26, 2026

First Posted

March 3, 2026

Study Start (Estimated)

August 31, 2026

Primary Completion (Estimated)

September 30, 2030

Study Completion (Estimated)

September 30, 2032

Last Updated

May 8, 2026

Record last verified: 2026-05

Locations