High Grade GliomaPhase 1NCT04254419
Phase 1 Study of Locoregional Injections of Ex Vivo Expanded Natural Killer Cells
A Phase 1 study testing NK cells in people with High Grade Glioma, run by Nationwide Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 39 years
- Conditions the study is for
- High Grade Glioma
- What is being tested?
- NK cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2025to Oct 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Clelie Peck, 614-722-5634, Clelie.Peck@nationwidechildrens.org
Sara Khan, MD
About this study
Official title: 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
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.
Read the detailed description
A cycle is 28 days (4 weeks) consisting of weekly infusions of UD TGFβi NK cells via Ommaya or a programable ventriculoperitoneal (VP) shunt for three weeks followed by one week of rest. The dose-limiting toxicity (DLT) period is the first 28 days (4 weeks). A DLT is defined as any event that is at least possibly attributable to the TGFβi NK cell product and that occurs from the time of initial NK cell infusion through the end of the first cycle (28 days). Patients with stable or improved disease will receive up to 12 cycles of TGFβi NK cell infusions.
- Conditions
- High Grade Glioma
- Being tested
- NK cells
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Measured: 36 months
Secondary outcomes (1)
Define tumor activity in children
To preliminarily define the antitumor activity in children with recurrent, refractory, or progressive primary malignant CNS tumors with the exception of diffuse midline gliomas and or diffuse intrinsic pontine glioma as measured by objective response rate (ORR) of UD TGFβi NK cells within the confines of a Phase I study.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start4 Mar 2025
- Primary completion31 Dec 2030 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade GliomaStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sara Khan, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04254419
- Sponsor's protocol ID
- STUDY00000659
- Status last verified
- Mar 2025
- First submitted
- 31 Jan 2020
- Last updated
- 13 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04254419
- Acronym / sponsor ID
- STUDY00000659
- Conditions
- High Grade Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- 4 Mar 2025 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- Oct 2031 (estimated)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A cycle is 28 days (4 weeks) consisting of weekly infusions of UD TGFβi NK cells via Ommaya or a programable ventriculoperitoneal (VP) shunt for three weeks followed by one week of rest. The dose-limiting toxicity (DLT) period is the first 28 days (4 weeks). A DLT is defined as any event that is at least possibly attributable to the TGFβi NK cell product and that occurs from the time of initial NK cell infusion through the end of the first cycle (28 days). Patients with stable or improved disease will receive up to 12 cycles of TGFβi NK cell infusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NK cell infusion | Experimental | Biological: NK cellsThe 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. |
Who may qualify
- Ages
- 12 months to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (33 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NK cellsThe 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. | Biological | NK cell infusion |
Primary outcome
Maximum tolerated dose or Recommended Phase 2 Dose (RP2D)
Time frame: 36 months
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).
Maximum tolerated dose
Time frame: 36 months
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
1 secondary outcome
Define tumor activity in children
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sara Khan, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NK cells in people with High Grade Glioma, run by Nationwide Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clelie Peck (614-722-5634, Clelie.Peck@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose or Recommended Phase 2 Dose (RP2D) (time frame: 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.