Phase 1 Study of Locoregional Injections of Ex Vivo Expanded Natural Killer Cells

NCT04254419 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00000659
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Each patient will receive up to 12 cycles of TGFβi NK cell infusions. Each cycle will be of 4 weeks duration. During the first 3 weeks, TGFβi NK cells will be infused once weekly. The 4th week will be a rest week. TGFβi NK cell infusions should be delivered at least 3 days apart (e.g., Friday of Week 1 and Monday of Week 2). Dose will be escalated in an inter-patient stepwise fashion consisting of 3 dose levels.

Conditions

High Grade Glioma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose or Recommended Phase 2 Dose (RP2D)

  To determine the maximum tolerated dose (MTD) and/or the RP2D of UD TGFβi NK cells that have been propagated ex vivo with genetically modified feeder cells and administered using an Ommaya reservoir (into tumor cavity) or a programable ventriculoperitoneal shunt (intraventricular).

  36 months

• Maximum tolerated dose

  To establish the maximum tolerated dose (MTD) of autologous natural killer cells that have been propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral via Ommaya reservoir in patients with recurrent high-grade glioma. MTD will be the maximum dose at which fewer than one-third of patients experience a dose-limiting toxicity during cycle 1 of therapy

  36 months

Secondary Outcomes (1)

• Define tumor activity in children

  6 months

Other Outcomes (5)

• NK cell antitumor activity

  36 months

• Assessment of the immuno-phenotype of expanded NK cells for high-grade glioma patients

  36 months

• Assessment of health-related quality-of-life of patients using patient reported outcomes measurement information system (PROMIS)

  36 months

Study Arms (1)

NK cell infusion

EXPERIMENTAL

The TGFβi NK cell product on this trial will be manufactured in the Cell Based Therapy (CBT) Core facility at Nationwide Children's Hospital. Donors have been identified with specific universal-donor NK cell characteristics. The NK cells are collected from these donors via apheresis and then undergo CD3 depletion followed by a 2-week expansion. TGFβi NK cells are then generated by weekly stimulation with feeder cells and cultured in IL-2 and TGFβ. After 2 weeks, the TGFβi NK cells are washed and cryopreserved for future use. The expanded donor NK cell product will be manufactured prior to subject enrollment. Patients will receive 3 cycles of NK cell infusions over 12 weeks. Each cycle will consist of three weekly injections followed by a rest week (week 4). If patients have stable or improved disease and additional doses are available, patients may continue to receive therapy for a total of 12 cycles.

Biological: NK cells

Interventions

NK cells BIOLOGICAL

The universal donor TGFβi NK cells will be cryopreserved until they are delivered bedside for infusion. The trained staff will thaw the product by the bedside. The administration of the cells will be done via an Ommaya intra-cavitary/a programable ventriculoperitoneal (VP) shunt. Once the infusion is ready for administration patients will be admitted to the infusion unit for monitoring. NK cells will be administered through the Ommaya/VP shunt in approximately 3 milliliters over approximately 2-5 minutes; followed by 1.5-2 milliliter preservative-free normal saline flush over approximately 1 minute.

NK cell infusion

Eligibility Criteria

• Age: 12 Months - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Sara Khan, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clelie Peck

CONTACT

614-722-5634; Clelie.Peck@nationwidechildrens.org

Lauren Rayman

CONTACT

614-722-3729; lauren.rayman2@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 5, 2020
• Study Start: March 4, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): October 1, 2031
• Last Updated: May 13, 2025

Record last verified: 2025-03

Locations

US (1)