The Efficacy and Safety of Brain-targeting Immune Cells (EGFRvIII-CAR T Cells) in Treating Patients With Leptomeningeal Disease From Glioblastoma. Administering Patients EGFRvIII -CAR T Cells May Help to Recognize and Destroy Brain Tumor Cells in Patients

NCT05063682 | Unknown Phase 1 DMC

• 1 other identifier: 6678EGFRvIII
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 3

Brief Summary

This phase I trial investigates the efficacy and safety of brain-targeting epidermal growth factor receptor chimeric antigen receptor immune cells (EGFRvIII-CAR T cells) in treating patients with leptomeningeal disease from glioblastoma. T cells are part of the immune system and help the body fight malignant tumours. Immune cells can be genetically modified to destroy brain tumor cells in the laboratory. EGFRvIII -CAR T cells are brain tumor specific and can enter and express its genes in immune cells. Administering patients EGFRvIII -CAR T cells may help to recognize and destroy brain tumor cells in patients with leptomeningeal disease from glioblastoma.

Conditions

Glioblastoma; Glioblastoma Multiforme; Glioma, Malignant

Keywords

Glioblastoma; CAR-T; EGFRvIII

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Up to 10 years

• Overall survival

  12 months

Secondary Outcomes (9)

• CAR (chimeric antigen receptor) T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)

  Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)

• Endogenous T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)

  Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)

• Cell phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)

  Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)

• Cytokine levels (Procartaplex panel) in PB, TCF and CSF

  Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)

• Disease response

  Up to 10 years

Study Arms (1)

Treatment

EXPERIMENTAL

Patients receive EGFRvIII -CAR T cells intracerebroventricular over 15 minutes on day 1. Patients may receive additional cycles based on the persistence of the cells.

Biological: EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes

Interventions

EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes BIOLOGICAL

ICV administration

Treatment

Eligibility Criteria

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

You may qualify if:

• Participant has been treated for leptomeningeal metastases after intrathecal chemotherapy and/or radiation OR refuses to undergo additional radiation and/or intrathecal chemotherapy
• Participant must have a Karnofsky performance status (KPS) \>= 60
• Participant must have a life expectancy of \>= 2 months
• Women of child-bearing potential must have negative serum pregnancy test and agree to use a reliable form of birth control prior to study entry and for at least two months following study treatment. Male research participants must agree to use a reliable form of birth control and not donate sperm during the study and for at least two months following study treatment
• Participant has a histologically confirmed EGFRvII+ (epidermal growth factor receptor) tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50)
• Participant or legal guardian must have the ability to understand and the willingness to sign a written informed consent

You may not qualify if:

• Research participant requires supplemental oxygen to keep saturation greater than 95%
• Research participant requires dialysis
• Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• Failure of research participant or legal guardian to understand the basic elements of the protocol and/or the risks/benefits of participating in the study.
• Participant is unwilling to stop treatment with chemotherapy or endocrine therapy and/or radiation one week prior and during the first 4 cycles of the study
• Participant has ventriculoperitoneal shunt
• Participant has a coagulopathy or bleeding disorder
• Participant is HIV+ (human immunodeficiency virus) or has acute CMV (cytomegalovirus) infection
• Participant has any uncontrolled illness, including ongoing or active infection; participant has known active hepatitis B or C infection; participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
• Participant has an autoimmune disease that requires constant treatment
• Participant has another active malignancy
• Participant is unable to undergo a brain magnetic resonance imaging (MRI)
• Participant is pregnant or breast feeding

Sponsors & Collaborators

• Chembrain LTD: lead
• University of Oulu: collaborator
• Jyväskylä Central Hospital: collaborator
• Apollo Hospital, New Delhi, India: collaborator

Study Sites (3)

Jyväskylä Central Hospital

Jyväskylä, Finland

Location

University Of Oulu

Oulu, Finland

Location

Apollo Hospital

New Delhi, India

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Condition Hierarchy (Ancestors)

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

Study Officials

• Kai Reinikainen, MD/PhD

  Chembrain LTD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2021
• First Posted: October 1, 2021
• Study Start: May 15, 2020
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: October 1, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1); FI (2)