Study Stopped
Enrollment on hold while reviewing a SAE.
Intra-Tumoral Injections of Natural Killer Cells for Recurrent Malignant Pediatric Brain Tumors
PNOC028
A Phase I Study of Intra-Tumoral Injections of Ex Vivo Expanded Natural Killer Cells in Children and Young Adults With Recurrent or Progressive Malignant Brain Tumors
2 other identifiers
interventional
24
1 country
10
Brief Summary
This phase I trial tests the safety, side effects, and best dose of ex vivo expanded natural killer cells in treating patients with cancerous (malignant) tumors affecting the upper part of the brain (supratentorial) that have come back (recurrent) or that are growing, spreading, or getting worse (progressive). Natural killer (NK) cells are immune cells that recognize and get rid of abnormal cells in the body, including tumor cells and cells infected by viruses. NK cells have been shown to kill different types of cancer, including brain tumors in laboratory settings. Giving NK cells from unrelated donors who are screened for optimal cell qualities and determined to be safe and healthy may be effective in treating supratentorial malignant brain tumors in children and young adults.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2024
Typical duration for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 24, 2023
CompletedFirst Posted
Study publicly available on registry
June 5, 2023
CompletedStudy Start
First participant enrolled
May 31, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
April 24, 2026
April 1, 2026
3.6 years
May 24, 2023
April 22, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Proportion of participants with treatment-emergent adverse events
Adverse events and clinically significant laboratory abnormalities (meeting grade 3, 4, or 5 criteria according to NCI CTCAE) will be summarized by maximum intensity and relationship to study drug(s). Grade 1 and 2 adverse events will be summarized if related to study therapy. Descriptive statistics will be utilized to display the data on toxicity seen. Toxicities will be summarized by tabulation in terms of type, grade and attribution for each dose level of each group of patients studied at the end of the trial.
From initiation of study treatment until 30 days from the end of therapy, approximately 1 year
Recommended Phase II dose (RP2D)
RP2D is defined as the dose level at which fewer than one-third of participants experience a dose limiting toxicity (DLT)
From initiation of study treatment until 30 days from the end of therapy, approximately 1 year
Study Arms (3)
Dose Level 2 (3x10^6) - Starting Dose
EXPERIMENTALEnrolled 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.
Dose Level 3 (3x10^7)
EXPERIMENTALIf 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.
Dose Level 4 (3x10^8)
EXPERIMENTALIf 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.
Interventions
Undergo placement of Ommaya reservoir
Imaging procedure
Ancillary studies
The TGFβi NK cell product will be manufactured in the Cell Therapy Laboratory at Nationwide Children's Hospital and given via infusion.
Eligibility Criteria
You may qualify if:
- Participants must have a histologically-confirmed recurrent or progressive malignant brain tumor including, but not limited to, infant-type hemispheric glioma, gliosarcoma, intracranial sarcoma and WHO Grade II ependymoma.
- Participants should be candidates for resection of the recurrent tumor and be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral; measurable residual tumor after surgery is not required for study entry. Pre-operative imaging needs to estimate that the resection cavity will be at least 2 cm x 2 cm in two dimensions for participants to be eligible.
- Given the lack of a standard of care treatment for children with recurrent or progressive malignant brain tumors, participants must have completed first-line treatment with radiation and/or chemotherapy prior to participating in this trial if applicable.
- All participants must be ≥ 1 year of age and ≤ 39 years of age at the time of entry into the study. The first 3 participants must be ≥ 8 years of age and ≤ 39 years of age at the time of entry into the study.
- Performance Score: Karnofsky ≥ 50 for participants \> 16 years of age and Lansky ≥ 50 for participants ≤ 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.
- Must have recovered from the acute toxic effects of prior therapy (i.e., NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade 1 or less)
- An interval of at least 12 weeks must have elapsed since the completion of radiation therapy.
- Chemotherapy/biologic therapy: All cytotoxic chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment (except 3 weeks for temozolomide and 6 weeks from last dose of nitrosoureas)
- Immunotherapy: The last dose of anti-tumor antibody therapy must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment
- For targeted agents only, participants should have recovered from any toxicity of the agent and have a minimum of 2 weeks since the last dose.
- For participants who have received prior bevacizumab, at least 4 weeks is required.
- Organ Function Requirements:
- Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) \>750/mm\^3.
- Platelet count \>75,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to registration).
- +13 more criteria
You may not qualify if:
- Tumor involvement that would require ventricular or brainstem injection or access through a ventricle or significant risk of ventricular penetration in order to deliver the TGFβi NK cells.
- Participants undergoing needle or open biopsy.
- Participants who are receiving any other investigational agents.
- Women of childbearing potential must not be pregnant or breast-feeding.
- Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.
- Any medical condition that precludes surgery.
- Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) \> 1.5 x ULN.
- Participants 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. If the medication can be discontinued \>1 week prior to NK cell infusion then the subject may be eligible following consultation with the Study Chairs.
- Participants with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, kidney disease or renal failure, organ transplantation, or significant psychiatric disorder.
- History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the participants ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems.
- Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sabine Mueller, MD, PhDlead
- CureSearchcollaborator
- Nationwide Children's Hospitalcollaborator
- Tommy Strong Foundationcollaborator
- Rally Foundationcollaborator
- Washington University School of Medicinecollaborator
Study Sites (10)
University of Alabama Birmingham
Birmingham, Alabama, 35294, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Johns Hopkins
Baltimore, Maryland, 21287, United States
Washington University in Saint Louis
St Louis, Missouri, 63130, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Seattle Children's
Seattle, Washington, 98105, United States
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sabine Mueller, MD, PhD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 24, 2023
First Posted
June 5, 2023
Study Start
May 31, 2024
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
De-identified participant data may be shared with collaborating researchers.