NK Cells for Glioblastoma

Overseen By Chibawanye Ene, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for recurrent glioblastoma, a type of brain cancer, using specially engineered NK cells. These cells, known as Engineered NK Cells containing IL13Ra and EGFvIII CAR, IL-21 secretion, and deleted TGF-BetaR2 and NR3C1, are designed to target and attack cancer cells. The trial aims to determine the best method to administer them directly to the tumor or through blood vessels. Individuals with a confirmed diagnosis of glioblastoma who have already undergone radiation and temozolomide treatment might be suitable candidates. Participants should have a single tumor no larger than 5 cm and must have completed prior treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must not be on immunosuppressive therapy within 7 days before joining the study. If you have used Avastin, a 12-week period without it is required before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that specially designed NK (natural killer) cells, tested for treating glioblastoma, appear safe. These NK cells, modified to include features like IL-21 secretion, are generally well-tolerated. In studies, patients received these cells safely, even in high doses, without serious side effects.

Researchers can administer the NK cells in various ways, such as directly into the tumor or through the brain's ventricles or arteries. Their safety has been tested in different situations, showing potential to fight tumors while remaining safe for patients.

As this is a Phase 1 trial, the main focus is on safety and determining the best delivery method. This means the treatment is still being tested for safety in humans. Overall, early findings suggest that engineered NK cells could be a safe treatment option for glioblastoma, but further research is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for glioblastoma, which typically involves surgery, radiation, and chemotherapy, this treatment utilizes engineered NK cells to target the tumor more precisely. These NK cells are enhanced with IL13Ra and EGFvIII CAR, which help direct them to the cancer cells. Additionally, they secrete IL-21 to boost immune response and have had TGF-BetaR2 and NR3C1 removed to improve their effectiveness. Researchers are excited because this approach could offer a more targeted and potentially less toxic alternative to traditional treatments, focusing the body's immune system directly on the tumor cells.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that specially designed natural killer (NK) cells could effectively treat glioblastoma, a type of brain cancer. These NK cells specifically target and destroy cancer cells. In this trial, participants will receive these engineered NK cells through intra-tumoral, intra-ventricular, or intra-arterial administration. Studies have found that NK cells engineered to produce IL-21 maintain their strong cancer-fighting abilities for an extended period. Additionally, NK cells with a special receptor called CAR, which targets a protein known as EGFRvIII, have demonstrated significant effects against glioblastoma cells. By removing a part called TGF-BetaR2, these NK cells remain active without being blocked by the tumor's defenses. Overall, these engineered NK cells offer a promising new approach for treating glioblastoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Chibawany Ene, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults (18+) with a specific type of brain cancer called recurrent glioblastoma or similar tumors, who have already had radiation and chemotherapy. Participants must have only one tumor under 5 cm, be in good physical condition, and have healthy blood counts, liver, and kidney function.

Inclusion Criteria

7. Adequate hematological function defined by white blood cell (WBC) count ≥ 3 x 10/L with absolute neutrophil count (ANC) ≥1.5 x109/L, lymphocyte count ≥ 0.5 x 109/L, platelet count ≥ 100 x 109/L, and Hgb ≥ 9 g/ dL (in absence of blood transfusion).

My liver tests are within the normal range required for the study.

I have a confirmed diagnosis of recurrent high-grade brain tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dual CAR Dual KO NK cells via intra-tumoral, intra-ventricular, or intra-arterial injection to determine the optimal route of administration

6-8 weeks

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety, adverse events, and response using RANO criteria

1 year

Regular visits for safety and efficacy assessments

What Are the Treatments Tested in This Trial?

Interventions

• Engineered NK Cells containing IL13Ra and EGFvIII CAR, IL-21 secretion and deleted TGF-BetaR2 and NR3C1

Trial Overview

The study is testing a new treatment where specially engineered natural killer (NK) cells are delivered directly to the brain tumor area in patients with recurrent glioblastoma. The goal is to find the best way to give this therapy safely.

How Is the Trial Designed?

Group I: Arm 3 Intra-arterial Experimental Treatment 1 Intervention

Will receive the NK cells as an intra-arterial administration .

Group II: Arm 2 Intra-Ventricular Experimental Treatment 1 Intervention

Will receive the NK cells as an intra-arterial administration

Group III: Arm 1 Intra-tumoral Experimental Treatment 1 Intervention

Will receive the NK cells as an intra-tumoral administration

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07579208

Study Details | NCT07579208 | A Phase1 ...

To find the best method of administering NK cells in patients with recurrent glioblastoma. Detailed Description. Primary Objectives. To ...

2.

clin.larvol.com

clin.larvol.com/trial-detail/NCT07579208

A Phase1 Clinical Trial Evaluating Locoregional Delivery ...

Publications for the trial NCT07579208.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6868035/

CAR-Engineered NK Cells for the Treatment of Glioblastoma

The NK cell therapy proved to be safe and partially effective, with two patients experiencing a partial response (PR), two patients a mixed response (MR) and ...

4.

mdanderson.org

mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2020-0960.html

A Phase I clinical trial with a window-of-opportunity ...

This phase I trial is to find out the best dose, possible benefits and/or side effects of engineered natural killer (NK) cells containing deleted TGF-betaR2 and ...

5.

targetedonc.com

targetedonc.com/view/the-promise-of-il-21-engineered-nk-cells-in-glioblastoma-treatment

The Promise of IL-21 Engineered NK Cells in Glioblastoma ...

We observed that IL-21 was particularly effective in maintaining the long-term cytotoxicity of NK cells. Our previous work had shown that ...

6.

hipa.ai

hipa.ai/study/NCT07579208

A Phase1 Clinical Trial Evaluating Locoregional Delivery ...

A Phase1 Clinical Trial Evaluating Locoregional Delivery Of Engineered NK Cells Containing IL13Ra And EGFvIII Chimeric Antigen Receptor (CAR), IL-21 Secretion ...