What side effects are associated with this type of intervention?

Common treatments for brain tumors, particularly those involving immune cell-mediated approaches like ex vivo expanded natural killer (NK) cells, can have several side effects. These may include immune-related adverse events such as inflammation, fever, fatigue, and flu-like symptoms. More severe side effects can involve neurotoxicity, leading to headaches, seizures, or cognitive changes. Additionally, there may be risks of infections due to immune system modulation. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of brain tumors. One notable example is the use of immune checkpoint inhibitors like nivolumab and pembrolizumab, which target PD-1/PD-L1 pathways to enhance the body's immune response against tumor cells. Additionally, bevacizumab, an anti-angiogenic agent, has been approved for recurrent glioblastoma. These treatments, while not identical, share a common goal with the ex vivo expanded natural killer cells trial: leveraging the immune system to target and eliminate tumor cells.

What other types of research exist?

Promising novel alternatives to Ex Vivo Expanded Natural Killer Cells for brain tumor patients include: 1) CAR-T cell therapy, which involves modifying a patient's T cells to target tumor-specific antigens; 2) Oncolytic virus therapy, which uses genetically modified viruses to selectively infect and kill tumor cells; 3) Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, which help to enhance the immune system's response against tumor cells; and 4) Tumor Treating Fields (TTF), a non-invasive treatment that uses electric fields to disrupt cancer cell division. These therapies are being actively researched and have shown potential in treating brain tumors.

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Cell Therapy

NK Cell Therapy for Pediatric Brain Cancer (PNOC028 Trial)

Phase 1

Recruiting

Research Sponsored by Sabine Mueller, MD, PhD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from initiation of study treatment until 30 days from the end of therapy, approximately 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial uses enhanced immune cells called natural killer cells to treat children and young adults with recurring or worsening brain tumors. The treatment involves injecting these cells directly into the tumor to help destroy cancer cells. Natural killer (NK) cells are a promising option in cancer immunotherapy, showing potential in treating various solid tumors, including brain tumors.

Who is the study for?

This trial is for children and young adults aged 1 to 39 with recurrent or progressive non-metastatic brain tumors (WHO Grade III/IV). They must have completed initial treatments, be fit for surgery to place an Ommaya reservoir, and not be on chronic steroids. Participants need proper organ function, a performance score of at least 50, and agree to use contraception. Excluded are those with immune disorders, severe illnesses, bleeding risks, pregnancy/breastfeeding or unstable conditions.

What is being tested?

The trial tests the safety and optimal dosage of NK cells from universal donors in treating malignant brain tumors that have returned after treatment. These NK cells are designed to fight tumor cells by being injected directly into the tumor site using an implanted reservoir.

What are the potential side effects?

Potential side effects may include reactions related to the immune system's response such as inflammation around the injection site or general flu-like symptoms. There could also be risks associated with surgical implantation of the Ommaya reservoir.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from initiation of study treatment until 30 days from the end of therapy, approximately 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from initiation of study treatment until 30 days from the end of therapy, approximately 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and from initiation of study treatment until 30 days from the end of therapy, approximately 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of participants with treatment-emergent adverse events

Recommended Phase II dose (RP2D)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Dose Level 4 (3x10^8)Experimental Treatment4 Interventions

If no safety or toxicity events are demonstrated by the previous dose cohort, enrolled participants in the next dosing cohort must proceed to surgery for tumor resection and Ommaya placement into the resection cavity within 14 days of enrollment. The dose of 3x10\^8 of TGFβi NK cells (first dose) may be administered at least 14 days after the Ommaya reservoir placement and may not start until all acute surgical complications have resolved (maximum of 6 weeks after enrollment). TGFβi NK cell infusions through the Ommaya reservoir will occur once weekly for three weeks followed by one rest week. If participants have stable or improved disease, participants may continue to receive therapy for a total of 3 cycles.

Group II: Dose Level 3 (3x10^7)Experimental Treatment4 Interventions

If no safety or toxicity events are demonstrated by the starting dose cohort, enrolled participants in the next dosing cohort must proceed to surgery for tumor resection and Ommaya placement into the resection cavity within 14 days of enrollment. The dose of 3x10\^7 of TGFβi NK cells (first dose) may be administered at least 14 days after the Ommaya reservoir placement and may not start until all acute surgical complications have resolved (maximum of 6 weeks after enrollment). TGFβi NK cell infusions through the Ommaya reservoir will occur once weekly for three weeks followed by one rest week. If participants have stable or improved disease, participants may continue to receive therapy for a total of 3 cycles.

Group III: Dose Level 2 (3x10^6) - Starting DoseExperimental Treatment4 Interventions

Enrolled participants must proceed to surgery for tumor resection and Ommaya placement into the resection cavity within 14 days of enrollment. Starting dose of 3x10\^6 of TGFβi NK cells (first dose) may be administered at least 14 days after the Ommaya reservoir placement and may not start until all acute surgical complications have resolved (maximum of 6 weeks after enrollment). TGFβi NK cell infusions through the Ommaya reservoir will occur once weekly for three weeks followed by one rest week. If participants have stable or improved disease, participants may continue to receive therapy for a total of 3 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging (MRI)

2015

Completed Phase 4

~1800

Implantation

2016

Completed Phase 4

~240

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immune cell-mediated therapies, such as Ex Vivo Expanded Natural Killer (NK) Cells, work by harnessing the body's immune system to target and eliminate tumor cells. NK cells are a type of immune cell that can recognize and destroy abnormal cells, including cancer cells, without prior sensitization. These cells are expanded and activated outside the body (ex vivo) to enhance their tumor-killing capabilities before being reintroduced into the patient. This approach is significant for brain tumor patients because it offers a targeted treatment option that can potentially overcome the limitations of traditional therapies like chemotherapy and radiation, which often have significant side effects and may not effectively penetrate the brain. By directly targeting tumor cells, immune cell-mediated therapies aim to improve treatment efficacy and patient outcomes.

Immunotherapy for Medulloblastoma: Current Perspectives.IDO1 Inhibition Synergizes with Radiation and PD-1 Blockade to Durably Increase Survival Against Advanced Glioblastoma.Immunotherapy and biological modifiers for the treatment of malignant brain tumors.