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AzTrials

GlioblastomaPhase 1CARTREMENDOUSNCT05063682

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

A Phase 1 study testing EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes in people with Glioblastoma and Glioblastoma Multiforme, run by Chembrain LTD at 3 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesin 2 countries
Study dates
15 May 2020to Oct 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Finland2 sites

  • Jyväskylä Central Hospital

    Jyväskylä

  • University Of Oulu

    Oulu

Other trials in Finland

India1 site

  • Apollo Hospital

    New Delhi

Other trials in India

About this study

Official title: A Phase 1 Study to Evaluate EGFRvIII -Targeted Chimeric Antigen Receptor (CAR) T Cells for Adult Patients With Leptomeningeal Glioblastoma

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.

Read the detailed description

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

Being tested
EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes
Keywords
Glioblastoma, CAR-T, EGFRvIII
Medical subject headings
Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    ICV administration

Study groups in NCT05063682
Study groupRoleWhat they receive
TreatmentExperimentalPatients receive EGFRvIII -CAR T cells intracerebroventricular over 15 minutes on day 1. Patients may receive additional cycles based on the persistence of the cells.
Receives: Biological: EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: Up to 10 years

  2. Overall survival

    Measured: 12 months

Secondary outcomes (9)

  1. 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

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

  2. 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

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

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

    Measured by absolute number per ul by flow

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

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

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

  5. Disease response

    Measured by Response Assessment in Neuro-Oncology Criteria (RANO LM).

    Measured: Up to 10 years

  6. Time to progression

    Progression defined by RANO LM criteria

    Measured: Up to 10 years

  7. Overall survival

    Measured: Up to 10 years

  8. CAR T and endogenous cells detected in tumor tissue

    Detected in tumor tissue by immunohistochemistry (IHC)

    Measured: Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)

  9. EGFRvII (epidermal growth factor receptor) antigen expression levels in tumor tissue.

    Descriptive statistics will be provided

    Measured: Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2021
  2. Study start15 May 2020
  3. Primary completionOct 2023 (estimated)
  4. Study completionOct 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05063682
Sponsor's protocol ID
6678EGFRvIII
Acronym
CARTREMENDOUS
Status last verified
Sep 2021
First submitted
10 Jun 2021
Last updated
1 Oct 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes in people with Glioblastoma and Glioblastoma Multiforme, run by Chembrain LTD at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Finland, India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 10 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05063682.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2021.

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