Actively Recruiting

Phase 1
Age: 12Years +
All Genders
ID04991870

A Phase I Clinical Trial of Engineered NK Cells Containing Deleted TGF-b2R2 and NR3C1 in Recurrent Grade 4 Astrocytoma (Glioblastoma)

Led by M.D. Anderson Cancer Center · Updated on 2026-01-23

25

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

Sponsors

M

M.D. Anderson Cancer Center

Lead Sponsor

N

National Cancer Institute (NCI)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating a new treatment using engineered natural killer (NK) cells called CB-NK-TGF-betaR2-/NR3C1- for patients with recurrent grade 4 astrocytoma, including glioblastoma. This phase I trial aims to find the safest dose, possible benefits, and side effects of these genetically modified immune cells that may help control the disease. The study also observes how these NK cells behave in the tumor environment and monitors immune responses during treatment. Participants will receive intratumoral injections of CB-NK-TGF-betaR2-/NR3C1- cells through an Ommaya catheter inserted into their brain. Treatment is given over 10 minutes followed by saline injection, repeated every four weeks for up to eight doses if there is no disease progression or unacceptable side effects. One group receives injections before and after surgical tumor removal, while another group receives injections without surgery. Throughout the study, participants undergo brain MRIs, immune cell monitoring, and various laboratory tests to track treatment effects and safety. Researchers evaluate tumor response using specific criteria and measure survival and progression timelines. The treatment period can last up to 32 weeks, with close monitoring for side effects and the activity of the NK cells in both blood and tumor tissue.

CONDITIONS

Brief Title

Phase I CB-NK-TGF-ßR2-/NR3C1- in rGBM

Who Can Participate

Age: 12Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed and dated informed consent.
  • Male or female participants aged 12 years or older.
  • Histologically confirmed supratentorial WHO grade 4 recurrent astrocytoma, including recurrent IDH wild-type glioblastoma or gliosarcoma and recurrent IDH-mutant grade 4 astrocytoma.
  • Prior radiation and temozolomide therapy received.
  • Karnofsky Performance Score (KPS) above 70; Lansky score above 70 if under 16 years old.
  • At least 12 weeks since conformal radiation unless early progression criteria met.
  • Baseline brain MRI with Advance Brain Tumor Imaging within 30 days before registration.
  • At least 3 weeks since surgery or 1 week since stereotactic biopsy and recovery from complications.
  • Adequate blood counts and organ function as specified.
  • Negative pregnancy test for females of childbearing potential.
  • Agreement to use effective contraception during and for 3 months after treatment.
  • For surgical group, at least 1 cm2 of resectable contrast-enhancing disease.
Not Eligible

You will not qualify if you...

  • Prior therapy with Gliadel or bevacizumab.
  • Prior interstitial brachytherapy or local chemotherapy injections.
  • Participation in another cancer investigational study within 4 weeks or plan to use Optune4 during trial.
  • Severe allergy to monoclonal antibodies or recent uncontrolled asthma.
  • Known HIV, active Hepatitis B or C infection.
  • Immunodeficiency or immunosuppressive therapy within 7 days prior.
  • Recent chemotherapy or targeted therapy within 2 weeks before treatment start.
  • Radiation therapy less than 12 weeks prior unless early progression.
  • Prior immune checkpoint inhibitors within 3 months.
  • Active second malignancy requiring treatment.
  • Tumors localized to brainstem or spinal cord, or with midline shift >0.5 cm.
  • Tumors larger than 5 cm in diameter.
  • Active autoimmune disease requiring systemic treatment or severe autoimmune history.
  • Interstitial lung disease or active pneumonitis.
  • Active infections requiring systemic therapy.
  • Psychiatric or substance abuse disorders interfering with trial participation.
  • Pregnancy, breastfeeding, or intending conception during study and 3 months after.
  • Recent live vaccine within 30 days.
  • Contraindications to MRI.
  • Bleeding disorders or use of full-dose anticoagulants that cannot be held.
  • Significant hemorrhage on baseline imaging.
  • Prior organ transplantation requiring immunosuppression.
  • Multicentric glioblastoma requiring distinct radiotherapy ports.

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 screening and enrollment visit

Treatment

Duration - Up to 8 doses administered every four weeks

Participants receive intratumoral injections of engineered natural killer cells (CB-NK-TGF-betaR2-/NR3C1-) via an Ommaya catheter every four weeks for up to 8 doses, depending on group assignment. Group 1 receives injections without surgery, while Group 2 involves catheter placement, surgery, and subsequent injections.

1 to 8 treatment visits spaced 4 weeks apart

Follow-up

Duration - Up to 6 months post-treatment

Participants are monitored for treatment response, safety, and survival outcomes for up to 6 months after treatment completion.

Visits as scheduled for assessments during follow-up period

Trial Site Locations

Total: 1 location

1

M D Anderson Cancer Center

Houston, Texas, United States, 77030

Actively Recruiting

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Research Team

S

Shiao-Pei Weathers, MD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

2

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