Locoregional injections of expanded natural killer cells for high grade glioma

Phase 1 Study of Locoregional Injections of Ex Vivo Expanded Natural Killer Cells in Children and Young Adults With Recurrent, Progressive, or Refractory Brain Tumors

This study is testing if giving special immune cells directly to patients with tough brain tumors can be safe and help them feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 12 Months to 39 Years
• Sex: All
• Sponsor: Nationwide Children's Hospital (Academic / other)
• Drugs / interventions: bevacizumab, Chemotherapy, Radiation
• Locations: 1 site (Columbus, Ohio)
• Trial ID: NCT04254419 on ClinicalTrials.gov

What this trial studies

This study involves administering up to 12 cycles of TGFβi NK cell infusions to patients with recurrent, refractory, or progressive malignant CNS tumors. Each cycle lasts 28 days, with weekly infusions for three weeks followed by a rest week. The study aims to evaluate the safety and tolerability of these infusions, with dose escalation occurring in a stepwise fashion across three levels. Patients will be monitored for dose-limiting toxicities during the first cycle.

Who should consider this trial

Good fit: Ideal candidates include patients with recurrent or progressive malignant CNS tumors who can tolerate the placement of an Ommaya reservoir or a programmable VP shunt.

Not a fit: Patients with diffuse midline gliomas or Diffuse Intrinsic Pontine Gliomas may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with high grade glioma who have limited treatment alternatives.

How similar studies have performed: While this approach is innovative, similar studies using NK cell therapies have shown promise, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

Diagnosis:

Recurrent, refractory, or progressive malignant CNS tumor

* Patients with a histologically confirmed diagnosis of a CNS tumor that is recurrent, progressive, or refractory with the exception of diffuse midline gliomas (DMG) or Diffuse Intrinsic Pontine Gliomas (DIPG). All tumors must have histologic verification at either the time of diagnosis or recurrence.
* Patients should be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral or a programable VP shunt.
* Measurable residual tumor after surgery is not required for study entry.
* Resection cavity needs to be at least 2 cm x 2 cm in two dimensions on imaging for patients deemed as candidates for an intratumoral infusion via an Ommaya reservoir.

  * Performance score: Lansky score of 50 or greater if ≤ 16 years of age or a Karnofsky score of 50 or greater if \> 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  * Adequate bone marrow function, without transfusion or growth factors within 21 days of NK cell administration.
  * Adequate liver function
  * Adequate Renal Function
  * Prothrombin time/international normalized ratio
  * Patients of child-bearing potential must agree to use adequate contraception
  * Adequate neurologic function defined

Prior Therapy:

* Chemotherapy

  * All patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days of nitrosourea.
  * For patients who have received prior bevacizumab, at least 6 weeks must have elapsed prior to enrollment.
* Biologic or investigational agent (anti-neoplastic, non-myelosuppressive):

  * Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 14 days prior to study enrollment.
  * For agents with known adverse events occurring beyond 14 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
  * At least 12 weeks since the completion of any immunotherapies or cell therapies.
* Radiation Therapy

  * Focal radiation therapy \> 6 weeks prior to enrollment.
  * Craniospinal irradiation \>12 weeks.
* Stem Cell Transplant.

Patient must be:

* ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease.
* ≥ 3 months since autologous stem cell transplant prior to enrollment.

  • Growth Factors
* Patients must be off all colony- forming growth factor(s) for at least 1 week prior to enrollment (e.g., filgrastim, sargramostim or erythropoietin).
* 2 weeks must have elapsed if patients received long-acting formulations.

  • Corticosteroids
* Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment.

Exclusion Criteria:

* Patients with intra- or extra-CNS metastasis or multi-focal disease.
* Patients with diffuse midline gliomas or Diffuse Intrinsic Pontine Gliomas (primary or recurrent).
* Pregnant or lactating patients.
* Participants who are receiving any other investigational agents.
* Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.
* Any medical condition that precludes surgery.
* Patients with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an auto- immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible.
* Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding.
* Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
* History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject's ability to participate

Where this trial is running

Columbus, Ohio

• Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Sara Khan, MD — Nationwide Children's Hospital
• Study coordinator: Clelie Peck

Conditions High Grade Glioma