Trial Title:
Intra-Tumoral Injections of Natural Killer Cells for Recurrent Malignant Pediatric Brain Tumors
NCT ID:
NCT05887882
Condition:
Pediatric Brain Tumor
Recurrent Pediatric Brain Tumor
Pediatric Supratentorial Neoplasm
Conditions: Official terms:
Neoplasms
Brain Neoplasms
Supratentorial Neoplasms
Recurrence
Mitogens
Conditions: Keywords:
Transforming growth factor beta imprinted
Natural Killer Cells
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Universal Donor (UD) Transforming growth factor beta imprinting (TGFβi) Natural Killer (NK) Cells
Description:
The TGFβi NK cell product will be manufactured in the Cell Therapy Laboratory at
Nationwide Children's Hospital and given via infusion.
Arm group label:
Dose Level 2 (3x10^6) - Starting Dose
Arm group label:
Dose Level 3 (3x10^7)
Arm group label:
Dose Level 4 (3x10^8)
Other name:
UD TGFβi NK cells
Other name:
UD TGFβi NK cell product
Intervention type:
Procedure
Intervention name:
Implantation
Description:
Undergo placement of Ommaya reservoir
Arm group label:
Dose Level 2 (3x10^6) - Starting Dose
Arm group label:
Dose Level 3 (3x10^7)
Arm group label:
Dose Level 4 (3x10^8)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging (MRI)
Description:
Imaging procedure
Arm group label:
Dose Level 2 (3x10^6) - Starting Dose
Arm group label:
Dose Level 3 (3x10^7)
Arm group label:
Dose Level 4 (3x10^8)
Other name:
MRI
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Dose Level 2 (3x10^6) - Starting Dose
Arm group label:
Dose Level 3 (3x10^7)
Arm group label:
Dose Level 4 (3x10^8)
Other name:
QOL Assessment
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.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of natural killer (NK) cells that have been
propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral
via an Ommaya reservoir in patients with recurrent or progressive supratentorial
malignant brain tumors.
II. To determine the recommended phase 2 dose (RP2D) for natural killer (NK) cells that
have been propagated ex vivo with genetically-modified feeder cells and administered
intra-tumoral via an Ommaya reservoir in patients with recurrent or progressive
supratentorial malignant brain tumors.
EXPLORATORY OBJECTIVES:
I. To determine the 6 months overall survival (OS), defined as the percentage of patients
in the study who are alive at 6 months following start of treatment.
II. To determine the persistence, immuno-phenotype and function of adoptively-transferred
expanded NK cells and correlate the findings with the overall response.
III. To determine the immune signature-based profile of each patient's tumor. IV. To
determine changes in the T-cell receptor (TCR) repertoire diversity before and after
Transforming growth factor beta imprinted (TGFβi) NK cell treatment.
V. To evaluate the effect of systemic steroids on the persistence and efficacy of TGFβi
NK cells.
VI. To assess Quality of Life (QOL) and cognitive measures in children and young adults
with recurrent or progressive supratentorial malignant brain tumors.
VII. To assess patient and/or proxy satisfaction with study participation via
patient-reported outcome (PRO) measures in the context of race ethnicity and other health
related social risks.
VIII. To assess on therapy toxicity in the context of race, ethnicity and other health
related social risks.
OUTLINE: This is a dose-escalation study.
Participants undergo placement of an Ommaya reservoir and receive universal donor
expanded TGF-beta-imprinted NK cells (TGFBi NK cells) intratumorally over 5 minutes via
Ommaya reservoir on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the
absence of disease progression or unacceptable toxicity. Participants also undergo
magnetic resonance imaging (MRI) of the brain during screening and on study and
collection of tumor-associated fluid via Ommaya reservoir on study. Participants may also
undergo MRI of the spine and lumbar puncture as clinically indicated.
Criteria for eligibility:
Criteria:
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/open biopsy 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.
Important note: The eligibility criteria listed above are interpreted literally and
cannot be waived.
Gender:
All
Minimum age:
1 Year
Maximum age:
39 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Aubrie Drechsler
Phone:
415-502-1600
Email:
PNOC028@ucsf.edu
Investigator:
Last name:
Sabine Mueller, MD, PhD
Email:
Principal Investigator
Start date:
May 31, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Sabine Mueller, MD, PhD
Agency class:
Other
Collaborator:
Agency:
Rally Foundation
Agency class:
Other
Collaborator:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Nationwide Children's Hospital
Agency class:
Other
Source:
University of California, San Francisco
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05887882
