RECRUITING

Intra-Tumoral Injections of Natural Killer Cells for Recurrent Malignant Pediatric Brain Tumors

Conditions

Pediatric Brain Tumor Recurrent Pediatric Brain Tumor Pediatric Supratentorial Neoplasm Transforming growth factor beta imprinted Natural Killer Cells

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase I Study of Intra-Tumoral Injections of Ex Vivo Expanded Natural Killer Cells in Children and Young Adults With Recurrent or Progressive Supratentorial Malignant Brain Tumors

Quick Facts

Study Start:2024-11-20

Study Completion:2027-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05887882

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 38 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants must have a histologically-confirmed recurrent or progressive, non-metastatic supratentorial World Health Organization (WHO) Grade III/IV malignant brain tumor. Including, but not limited to: anaplastic ependymoma, embryonal tumor, primitive neuroectodermal tumor, atypical teratoid rhabdoid tumor (ATRT), anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma, glioblastoma multiforme, gliosarcoma, or malignant glioma (NOS), WHO Grade II ependymoma. 2. 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 need to estimate that the resection cavity will be at least 2 cm x 2 cm in two dimensions for patients to be eligible. 3. Given the lack of a standard of care treatment for children with recurrent or progressive grade III/IV malignant brain tumors, participants must have completed first-line treatment with radiation and/or chemotherapy prior to participating in this trial. 4. 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. 5. 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. 6. 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. * At least 6 weeks since the completion of any cytotoxic chemotherapy regimen. * At least 12 weeks since the completion of any immunotherapies or cell therapies. * 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 6 weeks is required. 7. Organ Function Requirements: 1. 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 enrollment). 2. Adequate Renal Function Defined as: * A serum creatinine \<= 1.5 x upper limit normal (ULN) based on age/gender. 3. Adequate Liver Function Defined as: * Total bilirubin \<= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \<= 3 x ULN or direct bilirubin \<= 1.5 x ULN. * Alanine aminotransferase (ALT) \<= 3 x ULN. * Aspartate aminotransferase (AST) \<= 3 x ULN. 4. Adequate Neurologic Function Defined as: * Participants with seizure disorder may be enrolled if seizures are well-controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug. * Signs and symptoms of neurologic deficit must be stable for \>= 1 week prior to enrollment. 8. The effects of Transforming growth factor beta resistant (TGFβi) natural killer (NK) cells on the developing human fetus are unknown. For this reason and because TGFβi NK cells as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 6 months after completion of TGFβi NK cells administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 9. A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate. 10. Participants who are receiving dexamethasone must be on a stable or decreasing dose for 1-week prior to registration.	1. Participants with evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease, Cerebral spinal fluid (CSF) dissemination or extra-neural disease. 2. Tumor involvement that would require ventricular, brainstem or posterior fossa injection or access through a ventricle or risk of ventricular penetration in order to deliver the TGFβi NK cells. 3. Participants undergoing needle or open biopsy. 4. Participants who are receiving any other investigational agents. 5. Women of childbearing potential must not be pregnant or breast-feeding. 6. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions. 7. Any medical condition that precludes surgery. 8. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) \> 1.5 x ULN. 9. 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. 10. 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. 11. 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. 12. 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.

Inclusion Criteria

Exclusion Criteria

1. Participants must have a histologically-confirmed recurrent or progressive, non-metastatic supratentorial World Health Organization (WHO) Grade III/IV malignant brain tumor. Including, but not limited to: anaplastic ependymoma, embryonal tumor, primitive neuroectodermal tumor, atypical teratoid rhabdoid tumor (ATRT), anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma, glioblastoma multiforme, gliosarcoma, or malignant glioma (NOS), WHO Grade II ependymoma.
2. 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 need to estimate that the resection cavity will be at least 2 cm x 2 cm in two dimensions for patients to be eligible.
3. Given the lack of a standard of care treatment for children with recurrent or progressive grade III/IV malignant brain tumors, participants must have completed first-line treatment with radiation and/or chemotherapy prior to participating in this trial.
4. 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.
5. 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.
6. 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.
* At least 6 weeks since the completion of any cytotoxic chemotherapy regimen.
* At least 12 weeks since the completion of any immunotherapies or cell therapies.
* 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 6 weeks is required.
7. Organ Function Requirements:
1. 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 enrollment).
2. Adequate Renal Function Defined as:
* A serum creatinine \<= 1.5 x upper limit normal (ULN) based on age/gender.
3. Adequate Liver Function Defined as:
* Total bilirubin \<= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \<= 3 x ULN or direct bilirubin \<= 1.5 x ULN.
* Alanine aminotransferase (ALT) \<= 3 x ULN.
* Aspartate aminotransferase (AST) \<= 3 x ULN.
4. Adequate Neurologic Function Defined as:
* Participants with seizure disorder may be enrolled if seizures are well-controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.
* Signs and symptoms of neurologic deficit must be stable for \>= 1 week prior to enrollment.
8. The effects of Transforming growth factor beta resistant (TGFβi) natural killer (NK) cells on the developing human fetus are unknown. For this reason and because TGFβi NK cells as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 6 months after completion of TGFβi NK cells administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
9. A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
10. Participants who are receiving dexamethasone must be on a stable or decreasing dose for 1-week prior to registration.

1. Participants with evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease, Cerebral spinal fluid (CSF) dissemination or extra-neural disease.
2. Tumor involvement that would require ventricular, brainstem or posterior fossa injection or access through a ventricle or risk of ventricular penetration in order to deliver the TGFβi NK cells.
3. Participants undergoing needle or open biopsy.
4. Participants who are receiving any other investigational agents.
5. Women of childbearing potential must not be pregnant or breast-feeding.
6. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.
7. Any medical condition that precludes surgery.
8. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) \> 1.5 x ULN.
9. 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.
10. 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.
11. 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.
12. 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.

Contacts and Locations

Study Contact

Aubrie Dreschler

CONTACT

(415) 502-1600

PNOC028@ucsf.edu

Principal Investigator

Sabine Mueller, MD, PhD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Study Locations (Sites)

University of California, San Francisco

San Francisco, California, 94143

United States

Collaborators and Investigators

Sponsor: Sabine Mueller, MD, PhD

Sabine Mueller, MD, PhD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-11-20

Study Completion Date2027-12-31

Study Record Updates

Study Start Date2024-11-20

Study Completion Date2027-12-31

Terms related to this study

Keywords Provided by Researchers

Transforming growth factor beta imprinted
Natural Killer Cells

Additional Relevant MeSH Terms

Pediatric Brain Tumor
Recurrent Pediatric Brain Tumor
Pediatric Supratentorial Neoplasm