- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05063682
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 (CARTREMENDOUS)
A Phase 1 Study to Evaluate EGFRvIII -Targeted Chimeric Antigen Receptor (CAR) T Cells for Adult Patients With Leptomeningeal Glioblastoma
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
- 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.
- Determine the activity of EGFRvIII -CAR T cells based on survival rate at 12 months for both arms.
SECONDARY OBJECTIVES:
- 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
- Describe cytokine levels in PB, TCF, and CSF at applicable time points
- Estimate the rate of disease response by Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO LM) criteria
- Estimate rate of progression free survival at 6 months. Estimate rate of overall survival (OS) at 12 months by study arm.
- Estimate time to next treatment
- 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.
- 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
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
ICV administration
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 12 months
|
12 months
|
|
Incidence of adverse events
Time Frame: Up to 10 years
|
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
|
Up to 10 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Up to 10 years
|
Up to 10 years
|
|
CAR (chimeric antigen receptor) T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)
Time Frame: Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
|
Measured by absolute number per ul by flow
|
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)
Time Frame: Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
|
Measured by absolute number per ul by flow
|
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)
Time Frame: Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
|
Measured by absolute number per ul by flow
|
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
Time Frame: Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
|
Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
|
|
Disease response
Time Frame: Up to 10 years
|
Measured by Response Assessment in Neuro-Oncology Criteria (RANO LM).
|
Up to 10 years
|
Time to progression
Time Frame: Up to 10 years
|
Progression defined by RANO LM criteria
|
Up to 10 years
|
CAR T and endogenous cells detected in tumor tissue
Time Frame: Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)
|
Detected in tumor tissue by immunohistochemistry (IHC)
|
Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)
|
EGFRvII (epidermal growth factor receptor) antigen expression levels in tumor tissue.
Time Frame: Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)
|
Descriptive statistics will be provided
|
Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Kai Reinikainen, MD/PhD, Chembrain LTD
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 6678EGFRvIII
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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