Pilot Study of B7-H3 CAR-T in Treating Patients With Recurrent and Refractory Glioblastoma

NCT04385173 | Unknown Phase 1

• 1 other identifier: SAHZJU-BP102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot phase I study to evaluate the safety and efficacy on B7-H3 CAR-T in between Temozolomide cycles 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

Keywords

Chimeric Antigen Receptor (CAR)-T; Glioblastoma

Outcome Measures

Primary Outcomes (4)

• Incidence and type of adverse events

  Number of Participants With Treatment-Related Adverse Events and Types of adverse events as Assessed by CTCAE v4.0

  12 weeks

• Maximum tolerated dose (MTD)

  The highest dose of B7-H3 CAR-T that does not cause targeted dose limiting toxicity

  12 weeks

• Overall survival (OS)

  Kaplan Meier methods will be used to estimate median OS

  2 years, up to 15 years if necessary

• Progression-free survival (PFS)

  Kaplan Meier methods will be used to estimate median PFS. Progression is defined by Response Assessment in Neuro-Oncology (RANO) criteria

  2 years, up to 15 years if necessary

Secondary Outcomes (3)

• The pharmacokinetics (PK) of B7-H3 CAR-T

  12 weeks

• The pharmacokinetics (PK) of B7-H3 CAR-T

  12 weeks

• Disease response (ORR, CR, PR, DOR)

  2 years, up to 15 years if necessary

Other Outcomes (2)

• Cytokine levels in PB and CSF

  12 weeks

• T cell phenotype

  12 weeks

Study Arms (1)

B7-H3 CAR-T

EXPERIMENTAL

Patients will received regular cycles of Temozolomide treatment with 5 days of treatment and 23 days of interval. 3 infusions of B7-H3 CAR-T with 1-2 weeks of interval will be used in between cycles of Temozolomide treatment. Temozolomide treatment during B7-H3 CAR-T infusions will be stopped and resumed after CAR-T infusion.

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

Interventions

B7-H3 CAR-T DRUG

The B7-H3 CAR-T will be administrated via intratumoral or Intracerebroventricular injection through an Ommaya catheter in between Temozolomide cycles. Temozolomide will be stopped during the infusion of B7-H3 CAR-T

Also known as: BP102

B7-H3 CAR-T

Temozolomide DRUG

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.

Also known as: TMZ

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

You may not qualify if:

• Other active malignancy in the past 2 years except non-melanoma skin cancer, completely surgical removed low grade tumor, posttherapeutic 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

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• BoYuan RunSheng Pharma (Hangzhou) Co., Ltd.: collaborator

Study Sites (1)

the Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: May 12, 2020
• Study Start: December 1, 2022
• Primary Completion: March 1, 2024
• Study Completion: May 1, 2024
• Last Updated: December 28, 2022

Record last verified: 2022-12

Locations

CN (1)