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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)

Primary Purpose

Glioblastoma, Glioblastoma Multiforme, Glioma, Malignant

Status
Unknown status
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes
Sponsored by
Chembrain LTD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, CAR-T, EGFRvIII

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jyväskylä Central Hospital
  • University Of Oulu
  • Apollo Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of adverse events
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Overall survival

Secondary Outcome Measures

CAR (chimeric antigen receptor) T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)
Measured by absolute number per ul by flow
Endogenous T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)
Measured by absolute number per ul by flow
Cell phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)
Measured by absolute number per ul by flow
Cytokine levels (Procartaplex panel) in PB, TCF and CSF
Disease response
Measured by Response Assessment in Neuro-Oncology Criteria (RANO LM).
Time to progression
Progression defined by RANO LM criteria
Overall survival
CAR T and endogenous cells detected in tumor tissue
Detected in tumor tissue by immunohistochemistry (IHC)
EGFRvII (epidermal growth factor receptor) antigen expression levels in tumor tissue.
Descriptive statistics will be provided

Full Information

First Posted
June 10, 2021
Last Updated
September 30, 2021
Sponsor
Chembrain LTD
Collaborators
University of Oulu, Jyväskylä Central Hospital, Apollo Hospital, New Delhi, India
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1. Study Identification

Unique Protocol Identification Number
NCT05063682
Brief Title
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
Acronym
CARTREMENDOUS
Official Title
A Phase 1 Study to Evaluate EGFRvIII -Targeted Chimeric Antigen Receptor (CAR) T Cells for Adult Patients With Leptomeningeal Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 15, 2020 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chembrain LTD
Collaborators
University of Oulu, Jyväskylä Central Hospital, Apollo Hospital, New Delhi, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Glioblastoma Multiforme, Glioma, Malignant
Keywords
Glioblastoma, CAR-T, EGFRvIII

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes
Intervention Description
ICV administration
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame
Up to 10 years
Title
Overall survival
Time Frame
12 months
Secondary Outcome Measure Information:
Title
CAR (chimeric antigen receptor) T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)
Description
Measured by absolute number per ul by flow
Time Frame
Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
Title
Endogenous T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)
Description
Measured by absolute number per ul by flow
Time Frame
Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
Title
Cell phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)
Description
Measured by absolute number per ul by flow
Time Frame
Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days)
Title
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)
Title
Disease response
Description
Measured by Response Assessment in Neuro-Oncology Criteria (RANO LM).
Time Frame
Up to 10 years
Title
Time to progression
Description
Progression defined by RANO LM criteria
Time Frame
Up to 10 years
Title
Overall survival
Time Frame
Up to 10 years
Title
CAR T and endogenous cells detected in tumor tissue
Description
Detected in tumor tissue by immunohistochemistry (IHC)
Time Frame
Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)
Title
EGFRvII (epidermal growth factor receptor) antigen expression levels in tumor tissue.
Description
Descriptive statistics will be provided
Time Frame
Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kai Reinikainen, MD/PhD
Organizational Affiliation
Chembrain LTD
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jyväskylä Central Hospital
City
Jyväskylä
Country
Finland
Facility Name
University Of Oulu
City
Oulu
Country
Finland
Facility Name
Apollo Hospital
City
New Delhi
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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