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Dosi multiple di viroterapia con cellule staminali neurali (NSC-CRAd-S-pk7) per il trattamento dei gliomi ricorrenti di alto grado

2 novembre 2026 aggiornato da: City of Hope Medical Center

Uno studio di fase I su dosi multiple di viroterapia oncolitica basata su cellule staminali neurali (NSC-CRAd-S-pk7) somministrata per via intracerebrale a pazienti con gliomi ricorrenti di alto grado

This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence. NSC-CRAd-S-pk7 consists of neural stem cells that can target glioblastoma cells and carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

PRIMARY OBJECTIVE:

I. Determine the recommended maximum tolerated number of cycles (MTC) of intracavitary (ICT) administered neural stem cell-expressing CRAd-S-pk7 (NSCCRAd-S-pk7) for phase II testing based on dose-limiting toxicities (DLTs), the overall toxicity profile, and activity in patients with recurrent high-grade glioma (HGG).

II. Describe and compare the weekly dosing schedule (Treatment Schedule 4) to an every 2 week dosing schedule (Treatment Schedule 4a) of intracerebrally administered NSC-CRAd-S-pk7 based on DLTs, the overall toxicity profile, and activity in patients with glioblastoma at first recurrence.

III. Determine the recommended phase 2 dose schedule based on the overall toxicity profile, and activity in patients with recurrent high grade gliomas

SECONDARY OBJECTIVES:

I. I. Assess for evidence of biologic activity (cytotoxicity and anti-tumor immune responses) in posttreatment tissue samples.

II. Assess for the presence of NSC and/or CRAd-S-pk7 in post-treatment tissue samples.

III. Assess for possible development of antibody and T cell responses to the NSCs and/or CRAd-S-pk7 in CSF and blood.

IV. Assess for evidence of possible migration of NSCs and/or CRAd-S-pk7 outside of the brain and if so, determine if viral shedding is occurring.

V. Determine the persistence and intracerebral distribution of the NSCs and/or CRAd-S-pk7 whenever permission is given to perform a brain autopsy on a study participant.

VI. Estimate the rates of disease response, progression-free survival at 6 months (PFS6mo) and overall survival at 9 months (OS9mo) for all study participants and separately for the cohorts of glioblastoma patients at first recurrence treated at the MTC administered once a week or every 2 weeks.

VII. Identify a molecular signature of vulnerability for predicting which glioma patients will benefit most from treatment with NSC-CRAd-S-pk7.

VIII. Describe and compare changes in immunosuppressive and immunostimulatory cytokines in CSF from study participants enrolled to Treatment Schedules 4 and 4a.

IX. Assess for the presence of exhausted T cell phenotypes in CSF samples and compare the degree of T cell exhaustion in study participants enrolled to Treatment Schedules 4 and 4a.

OUTLINE:

Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks via a catheter placed during surgery. A second catheter is placed in the cerebral ventricle to obtain serial samples of CSF for correlative studies. Two weeks after the last dose of study agent is administered, study participants undergo a second surgical procedure to remove the catheters and obtain post-treatment tissue samples for analysis.

FINANCIAL ASSISTANCE:

There is funding to help with the cost of transportation, lodging, and meals for participants who qualify for financial assistance.

Tipo di studio

Interventistico

Iscrizione (Stimato)

36

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • California
      • Duarte, California, Stati Uniti, 91010
        • Reclutamento
        • City of Hope Medical Center
        • Contatto:
        • Investigatore principale:
          • Jana L. Portnow, MD
      • Stanford, California, Stati Uniti, 94305
    • Illinois
      • Chicago, Illinois, Stati Uniti, 60611
        • Sospeso
        • Northwestern University
    • North Carolina
      • Winston-Salem, North Carolina, Stati Uniti, 27109
        • Non ancora reclutamento
        • Wake Forest University
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Patient must be age >= 18 years

  • Patient has a Karnofsky performance status of >= 70%

  • Patient has a life expectancy of >= 3 months

    • When determining the maximum tolerated number of treatment cycles (MTC): patient has a histologically confirmed diagnosis of a grade 3 or 4 glioma (eg., glioblastoma, grade 4 astrocytoma, grade 3 astrocytoma, grade 3 oligodendroglioma). (This part of the study has been completed).
    • When enrolling to Treatment Schedules 4 and 4a: patient has glioblastoma at first recurrence.

  • Imaging studies show evidence of recurrent, supratentorial tumor(s).

  • Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide

  • The patient must be in need of surgery for tumor resection

  • Based on the neurosurgeon's judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles

  • Absolute neutrophil count (ANC) of >= 1000 cells/mm^3

  • Platelet count >= 100,000 cells/mm^3

  • Total bilirubin =< 2.0 mg/dl

  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 4 times the institutional upper limit of normal

  • Serum creatinine =< the institutional upper limit of normal

  • At least 2 weeks from taking the last dose of a targeted agent

  • At least 4 weeks from the last dose of bevacizumab For temozolomide, an interval of 23 days is required from the last dose administered if the patient was recently treated with adjuvant temozolomide, consisting of temozolomide daily for 5 days, repeated every 28 days.

  • At least 2 weeks from taking the last dose of a targeted agent.

  • At least 4 weeks from the last dose of bevacizumab.

  • All significant toxicities from previous anticancer therapy must have stabilized to a new baseline or resolved.

  • All participants must have the ability to understand and the willingness to sign a written informed consent.

  • The effects of this treatment on a developing fetus are unknown. Therefore, female patients of childbearing potential and sexually-active male patients or who are able to impregnate their partner, must agree to use an effective method of contraception while participating in this study. Patients of childbearing potential must have a negative pregnancy test =< 2 week prior to registration.

Exclusion Criteria:

  • Patient has multi-focal disease.
  • Patient is receiving radiation, chemotherapy, or another investigational agent.
  • Patient has had prior therapy with neural stem cells.
  • Patient has not recovered from any toxicity (> grade 1) of prior therapies, except alopecia.
  • Patient is unable to undergo a brain MRI.
  • Patient has chronic or active viral infections of the central nervous system (CNS).
  • Patient has a coagulopathy or bleeding disorder.
  • Patient has an uncontrolled illness including ongoing or active infection.
  • Patient has another active malignancy.
  • Patient is pregnant or breastfeeding.
  • A patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Treatment (NSC-CRAd-S-pk7)

Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks (depending on when they enroll in the study) via a catheter that was placed during surgery
Procedura: Resection

Undergo surgical resection

Altri nomi:
  • Somministrazione intracerebrale di NSC-Crad-S-PK7 tramite catetere intracavitario
  • Rimozione dei campioni di CSF tramite un catetere posto nel ventricolo cerebrale laterale
Biologico: Neural Stem Cells-expressing CRAd-S-pk7

Given intracerebrally

Altri nomi:
  • NSC caricati con CRAd-S-pk7
  • NSC-CRAd-S-pk7
  • NSC-CRAd-S-pk7 Viroterapeutico
  • SC-CRAd-Survivin-pk7

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Incidence of adverse events
Lasso di tempo: Up to 30 days post removal of Rickhams

Assessed using the Common Terminology Criteria for Adverse Events version 5.0.
Up to 30 days post removal of Rickhams
Progression-free survival (PFS)
Lasso di tempo: From the time of surgery to the event date of progression, assessed at 6 months]

Will estimate the rate 90% confidence interval (CI) for PFS at 6 months and use Kaplan Meier methods to estimate median PFS for all study participants as well as for the cohorts of glioblastoma (GBM) participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 given once a week or every two weeks.
From the time of surgery to the event date of progression, assessed at 6 months]

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Immunogenicità delle cellule staminali neurali che esprimono CRAd-S-pk7 (NSC-CRAd-S-pk7)
Lasso di tempo: Fino a 30 giorni dopo la rimozione di Rickham
Fino a 30 giorni dopo la rimozione di Rickham
Valutato utilizzando i test immunologici multiplex nei campioni di liquido cerebrospinale (CSF) e sequenziamento dell'RNA in campioni di CSF, sangue periferico e tessuto tumorale.
Lasso di tempo: Fino a 30 giorni dopo la rimozione di Rickhams
Fino a 30 giorni dopo la rimozione di Rickhams
NSC-CRAd-S-pk7 migration within the brain
Lasso di tempo: Up to 30 days post removal of Rickhams

Neural stem-cells and/or free viral particles will be assessed in samples of post-treatment tissue samples.
Up to 30 days post removal of Rickhams
NSC-CRAd-S-pk7 migration outside the brain
Lasso di tempo: Up to 30 days post removal of Rickhams

4. Neural stem-cells and/or free viral particles will be assessed in samples of CSF, peripheral blood, urine, oral and rectal mucosa (via swabbing), and skin at the injection site (also via swabbing).
Up to 30 days post removal of Rickhams
Disease response
Lasso di tempo: Up to 2 years

Response Assessment in Neuro-Oncology Criteria will be used to assess response on brain magnetic resonance imaging in all study participants who receive at least 80% of the planned doses of study treatment. Disease response will be similarly assessed for the cohorts of GBM participants at first recurrence who will be treated with 4 doses of NSC-CRAD-S-pk7 once a week or every two weeks.
Up to 2 years
Overall survival (OS)
Lasso di tempo: From time of surgery to date of death, assessed at 9 months

Will estimate the rate 90% CI for OS at 9 months and use Kaplan Meier methods to estimate median OS for all study participants as well as for the cohorts of GBM participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 once a week or every two weeks.
From time of surgery to date of death, assessed at 9 months
Changes in HSPG and survivin expression
Lasso di tempo: Baseline up to 2 years

Changes in survivin expression by immunohistochemistry IHC in pre- and post-treatment tissue to see if there is a relationship with disease response.
Baseline up to 2 years
Changes in immune cell populations
Lasso di tempo: Baseline up to 2 years

Changes in immune cell populations in the tumor microenvironment in pre- and post-treatment tumor tissue samples will be assessed by Vectra Spectral Imaging.
Baseline up to 2 years
Changes in tumor growth
Lasso di tempo: Baseline up to 2 years

Develop a biomathematical model for predicting tumor response to study treatment.
Baseline up to 2 years

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

City of Hope Medical Center

Collaboratori

National Cancer Institute (NCI)

Investigatori

  • Investigatore principale: Jana L Portnow, MD, City of Hope Medical Center

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

2 maggio 2023

Completamento primario (Stimato)

7 febbraio 2028

Completamento dello studio (Stimato)

7 febbraio 2028

Date di iscrizione allo studio

Primo inviato

22 novembre 2021

Primo inviato che soddisfa i criteri di controllo qualità

22 novembre 2021

Primo Inserito (Effettivo)

1 dicembre 2021

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

4 novembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

2 novembre 2026

Ultimo verificato

1 novembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 22338
  • P30CA033572 (Sovvenzione/contratto NIH degli Stati Uniti)
  • 22338 (Altro identificatore: City of Hope Medical Center)
  • NCI-2022-10170 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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