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

S
Scott Coven

Primary Investigator

Enrolling By Invitation
1 years - 38 years
All
Phase 1
2 participants needed
2 Locations

Brief description of study

What is this study about?
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.
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the study?
  • This is a dose-escalation study.  Participants undergo placement of an Ommayavoir and receive universal donor expanded TGF-beta-imprinted NK cells (TGFBi NK cells) intratumorally via Ommaya reservoir in 4-week cycles.
  • Infusions via Ommaya will occur once weekly for three weeks followed by one week of rest.
  • If patients have stable or improved disease, patients may continue to receive therapy for a total of 12 cycles.
  • Participants will be followed for 5 years after completion of treatment, or until removal from study or death, whichever comes first.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Pediatric Brain Tumor, Pediatric Supratentorial Neoplasm, Riley
  • Age: 1 years - 38 years
  • Gender: All

Inclusion 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.

Exclusion Criteria:

  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.
     

Updated on 25 Feb 2025. Study ID: PHO-UCSF-PNOC028, 22245
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