B7-H3 CAR-T for Recurrent or Refractory Glioblastoma

NCT04077866 | Unknown Phase 1

• 1 other identifier: SAHZJU-RCT-BP102
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

This is a randomized, parallel-arm, phase I/II study to evaluate the safety and efficacy of B7-H3 CAR-T in between Temozolomide cycles comparing to Temozolomide alone in treating patients with glioblastoma that has come back or does not respond to the standard treatment. The antigen B7-H3 is highly expressed in glioblastoma of a subset of patients. B7-H3 CAR-T, made from isolated patient peripheral blood mononuclear cells, can specifically attack patient glioblastoma cells that expressing B7-H3.

Conditions

Recurrent Glioblastoma; Refractory Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Kaplan Meier methods will be used to estimate median OS

  2 years, up to 15 years if necessary

Secondary Outcomes (6)

• Incidence and type of adverse events

  12 weeks

• Maximum tolerated dose (MTD)

  12 weeks

• Progression-free survival (PFS)

  2 years, up to 15 years if necessary

• Peak Concentration (Cmax) of B7-H3 CAR-T

  12 weeks

• Area under the concentration versus time curve (AUC) of B7-H3 CAR-T

  12 weeks

Other Outcomes (2)

• Cytokine levels in PB and CSF

  12 weeks

• T cell levels and phenotype

  12 weeks

Study Arms (2)

Temozolomide alone

ACTIVE COMPARATOR

Temozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped.

Drug: Temozolomide

Temozolomide + B7-H3 CAR-T

EXPERIMENTAL

Temozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped. The B7-H3 CAR-T will be administrated via intratumoral or Intracerebroventricular injection through an Ommaya catheter in between Temozolomide cycles. Temozolomide treatment in the cycles of B7-H3 CAR-T treatment will be stopped.

Drug: Temozolomide; Biological: B7-H3 CAR-T

Interventions

Temozolomide DRUG

Temozolomide is an FDA-approved drug that is given to patients

Also known as: TMZ

Temozolomide + B7-H3 CAR-T; Temozolomide alone

B7-H3 CAR-T BIOLOGICAL

B7-H3-targeting CAR-T cells derived from patient own peripheral blood mononuclear cells will be given to patients via intracerebral injection though an Ommaya catheter

Temozolomide + B7-H3 CAR-T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative.
• Histologically confirmed diagnosis of World Health Organization (WHO) classification grade IV glioblastoma (GBM).
• Clinical Pathology confirms B7-H3 positive tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50).
• Relapsed/refractory disease confirmed by radiographic evidence after standard therapy.
• Suitable for the surgery of the placement of the Ommaya catheter.
• Eastern Cooperative Oncology Group (ECOG) =0 or 1 (need to be confirmed before intratumoral or intracerebroventricular injection)
• \>= 8 weeks after completion of front-line radiation therapy
• \>= 6 weeks after completion of nitrourea chemotherapy
• \>= 14 days after completion of Temozolomide or other chemotherapy
• weeks of wash-out time after completion of targeted therapy with related adverse events (AE) on baseline (4 weeks for Bevacizumab). Patients with other chronic AEs are in the investigator's judgement
• Blood cell count： White blood count (WBC) \>= 2000/μL；Neutrophil count \>= 1500/μL；Platelets \>= 100 x 103/μL；Hemoglobin \>= 9.0 g/dL
• Serum Creatinine \<= 1.5×ULN or Creatinine Clearance Rate (Cockcroft and Gault) \> 30 mL/min/1.73 m2
• Alanine Transaminase (ALT) \<= 5×ULN and total bilirubin \< 2.0mg/dL
• Lung function: Oxygen (O2) saturation \>= 92% on room air and \< CTCAE grade 1 dyspnea
• Heart function: Left ventricular ejection fraction (LVEF) \>= 40% by multigated acquisition (MUGA) scan or echocardiogram

You may not qualify if:

• Other active malignancy in the past 2 years except non-melanoma skin cancer, completely surgical removed low grade tumor, post-therapeutic limited-stage prostate cancer, biopsy confirmed in situ cervical carcinoma, PAP test confirmed squamous intraepithelial lesions
• Participant is undergoing or planning to take other anti-tumor therapies
• Participant is systematic steroid-dependent, or is expecting to be treated with systematic steroid
• Active immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus infection
• Active infection from fungi, bacteria and/or viruses
• Known history of the following cardiac diseases in the past 6 months: New York Heart Association (NYHA) defined grade III or IV heart failure, cardiac angioplasty, myocardial infarction, unstable angina and other clinically significant heart diseases
• Known history and/or clinically evident central nerve system diseases: seizure, epileptic seizure, aphasia, paralysis, stroke, severe brain damage, dementia, Parkinson's Disease, cerebellar diseases, organic brain syndrome and psychiatric disorders
• Autoimmune diseases
• Pregnant or breastfeeding females
• Therapeutic doses of corticosteroid within 7 days before leukapheresis or 72 hours before B7-H3 CAR-T infusion
• Cytotoxic chemotherapy without lymphocytotoxicity within 1 week before leukapheresis except that the treatment has been stopped for more than 3 half-lives of the drug
• Lymphocytotoxic chemotherapy (cyclophosphamide, Ifosfamide and bendamustine) within 2 weeks before leukapheresis
• Other clinical trials drugs within 4 weeks before leukapheresis except that the drug has no effect or the disease has progressed, and the treatment has been stopped for more than 3 half-lives of the drug
• Radiotherapy within 6 weeks before leukapheresis
• Prior trials of CAR-T or other cell therapy

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Ningbo Yinzhou People's Hospital: collaborator
• Huizhou Municipal Central Hospital: collaborator
• BoYuan RunSheng Pharma (Hangzhou) Co., Ltd.: collaborator

Study Sites (3)

the Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

Huzhou Central Hospital

Huzhou, Zhejiang, 313003, China

NOT YET RECRUITING

Ningbo Yinzhou People's Hospital

Ningbo, Zhejiang, 315040, China

NOT YET RECRUITING

Related Publications (1)

• Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.

  PMID: 35468680 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Jianmin Zhang, MD

CONTACT

+86-13805722695; 2307010@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: September 4, 2019
• Study Start: June 1, 2023
• Primary Completion: June 1, 2025
• Study Completion: August 1, 2025
• Last Updated: December 28, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)