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

NCT ID: NCT05063682

Last Updated: 2021-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-15

Study Completion Date

2023-10-31

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

1. Examine and describe the safety and feasibility of EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes (EGFRvIII -CAR T cells) through intracerebroventricular (ICV) delivery as adjuvant therapy in participants with EGFRvIII+ leptomeningeal disease from glioblastoma.
2. Determine the activity of EGFRvIII -CAR T cells based on survival rate at 12 months for both arms.

SECONDARY OBJECTIVES:

1. Describe persistence, expansion and phenotype of endogenous and EGFRvIII -CAR T cells in peripheral blood (PB), tumor cyst fluid (TCF) and cerebral spinal fluid (CSF) at applicable time points
2. Describe cytokine levels in PB, TCF, and CSF at applicable time points
3. Estimate the rate of disease response by Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO LM) criteria
4. Estimate rate of progression free survival at 6 months. Estimate rate of overall survival (OS) at 12 months by study arm.
5. Estimate time to next treatment
6. Evaluate EGFRvIII -CAR T cell persistence in the tumor tissue and the location of the EGFRvIII -CAR T cells with respect to the infusion site.
7. Evaluate biomarkers and cytokine levels

OUTLINE:

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. The patients are followed extensively according to the clinical pharmacology sampling plan; on days 1-30, months 2-12, and three times per year up to 10 years based on response

Conditions

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Glioblastoma Glioblastoma Multiforme Glioma, Malignant

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment

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.

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

ICV administration

Interventions

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

ICV administration

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oulu

OTHER

Sponsor Role collaborator

Jyväskylä Central Hospital

OTHER

Sponsor Role collaborator

Apollo Hospital, New Delhi, India

OTHER

Sponsor Role collaborator

Chembrain LTD

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kai Reinikainen, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Chembrain LTD

Locations

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Jyväskylä Central Hospital

Jyväskylä, , Finland

Site Status

University Of Oulu

Oulu, , Finland

Site Status

Apollo Hospital

New Delhi, , India

Site Status

Countries

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Finland India

Other Identifiers

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6678EGFRvIII

Identifier Type: -

Identifier Source: org_study_id

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