Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma

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Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma

Study Purpose

The goal of this clinical trial is to learn about the safety and feasibility of administering repeated doses of neural stem cell (NSC)-conditionally replicative adenovirus (CRAd)-survivin (S)-protomer (p)k7, in persons with newly diagnosed high grade glioma. The main questions it aims to answer are:

- whether multiple doses of NSC-CRAd-S-pk7 are safe and feasible.

- how multiple doses of NSC-CRAd-S-pk7 influence tumor response, overall survival, time to tumor progression, and quality of life.

Participants will:

- undergo a biopsy to confirm high grade glioma, then receive the first dose of NSC-CRAd-S-pk7 into the brain.

- about 2 weeks later, undergo surgery to remove the tumor and receive the second dose of NSC-CRAd-S-pk7 into the brain.

- start chemoradiation about 2 weeks after surgery, then about 2 weeks later, receive the 3rd dose of NSC-CRAd-S-pk7 into the brain.

- four weeks later, at the end of chemoradiation, receive a fourth dose of NSC-CRAd-S-pk7 into the brain.

- after radiation is finished, receive standard of care chemotherapy and tumor-treating fields.

Two additional doses of NSC-CRAd-S-pk7 will be given every 4 weeks. Every other patient enrolled will receive N-acetylcysteine amide (NACA), from registration until the day prior to surgery and the second dose of NSC-CRAd-S-pk7.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Diagnosis of a high-grade glioma (WHO grade 3 or grade 4).

- Patients must have presumed high grade glioma (WHO grade 3 or 4) based on clinical and radiologic evaluation for registration.

- A pathologic confirmation of high grade glioma must be made at the time of stereotactic biopsy prior to NSC-CRAd-S-pk7 injection; if this is not possible, the injection will not be performed and the subject will no longer be eligible for the study).

- Tumor must be accessible for injection and must not be located in the brainstem or contained within the ventricular system.

- Planning to undergo standard radiation/chemotherapy.

- 18 years of age or older.

- Performance status (PS) must be WHO PS of < 2.

- Stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg/day for the 5 days prior to inclusion.

- Serum glutamic-oxaloacetic transaminase (SGOT or AST) < 3x upper limit of normal.

- Serum creatinine < 2mg/dl.

- Platelets > 100,000/mm3 and white blood cells (WBCs) > 3000/mm3.

Exclusion Criteria:

- Prior or ongoing liver disease including known cirrhosis.

- Known hepatitis B or C infection, known HIV infection.

- Chronic use of immunosuppressive drugs (with exception of corticosteroids required for mass effect).

- Acute viral, bacterial or fungal infections requiring therapy.

- Pregnant or breast-feeding patients.

- Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).

- Prior radiation therapy to the brain or prior treatment for brain tumor.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06169280
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Northwestern University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Roger Stupp, MD
Principal Investigator Affiliation	Northwestern University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioma, Malignant, New Diagnosis Tumor

Additional Details

The treatment regimen contains 3 phases: Surgical phase: Patients undergo a biopsy and upon intraoperative confirmation of high grade glioma, NSC-CRAd-S-pk7 dose #1 will be injected into the biopsy site. Patients will undergo resection of the tumor 14 (+/- 3) days later, administration of second dose of the investigational product (NSC-CRAd-S-pk7 dose #2), and implantation of the catheter system. The investigational product will then be given monthly for a total of 6 doses (see below). Every other patient enrolled (beginning with the first patient) will also undergo oral administration of NACA (an over-the-counter drug that acts as a free radical scavenger and improves NSC viability) starting at registration until the day prior to surgical tumor resection and planned investigational product injection #2. Radiotherapy phase: After recovery from surgery (usually within 2 weeks), standard chemoradiotherapy will be initiated consisting of daily radiotherapy (2 Gy per fraction x 30 fractions) and concomitant temozolomide (TMZ) chemotherapy (75 mg/m2 daily from day 1 of RT until last day of RT). About 10-14 days into radiotherapy (= approx. 4 weeks after intraoperative dose #2), patients will be receiving NSC-CRAd-S-pk7 dose #3 through the previously implanted catheter system. This also marks the beginning of the formal dose-limiting toxicity (DLT) period, as this virus' survivin gene promoter is activated by the concomitant irradiation. Four weeks later, ie. at the end of radiotherapy dose #4 is administered as previously, provided no DLT toxicity has been observed and viral treatment related toxicities have returned to grade ≤ 2. Adjuvant (also called maintenance) phase: As per standard of care, approx. 4 weeks after end of radiotherapy, patients will start maintenance TMZ chemotherapy (150

- 200 mg/m2, daily x 5 every 28 days) and loco-regional treatment with alternating Tumor Treating Fields (TTFields, Optune®).

NSC-CRAd-S-pk7 doses #5 and #6 will be administered concurrently (± 3 days) with adjuvant cycle 1 and 2 of TMZ.

Arms & Interventions

Arms

Experimental: NSC-CRAd-S-pk7

NSC-CRAd-S-pk7 1·50 x 10⁸ NSCs loaded with1·875 x viral particles administered intra-tumorally on Day 0 and Day 15, then every 4 weeks for up to 6 total doses.

Experimental: NSC-CRAd-S-pk7 + N-acetylcysteine amide (NACA)

NSC-CRAd-S-pk7 1·50 x 10⁸ NSCs loaded with 1·875 x viral particles administered intra-tumorally on Day 0 and Day 15, then every 4 weeks for up to 6 total doses. In addition, N-acetylcysteine amide (NACA) 600 mg oral, is taken daily from registration to just prior to dose 2 of NSC-CRAd-S-pk7.

Interventions

Biological: - NSC-CRAd-S-pk7

NSC-CRAd-S-pk7 1·50 x 10⁸ NSCs loaded with1·875 x viral particles administered intra-tumorally on Day 0 and Day 15, then every 4 weeks for up to 6 total doses.

Dietary Supplement: - N-acetylcysteine amide (NACA)

N-acetylcysteine amide (NACA) 600 mg oral, is taken daily from registration to just prior to dose 2 of NSC-CRAd-S-pk7.

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Christina Amidei, PhD

[email protected]

(312) 695-9124

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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