Advanced GliomaPhase 1NCT02331693
CAR T Cells in Treating Patients With Malignant Gliomas Overexpressing EGFR
A Phase 1 study testing anti-EGFR CAR T in people with Advanced Glioma, run by RenJi Hospital at 1 site in China.
Trial summary
The purpose of this study is to determine whether autologous T cells bearing chimeric antigen receptor that can specifically recognize EGFR overexpressed in tumor cells is safe and effective for patients with EGFR-overexpressing malignant glioma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Glioma
- What is being tested?
- anti-EGFR CAR T
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- Dec 2014to Dec 2016
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically proven glioblastomas or gliosarcomas that overexpress EGFR as assessed by IHC, FISH, western blot or RT-PCR.
- Patients must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered NED). This includes recurrent GBM after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy.
- Patients must either not be receiving steroids, or be on a stable dose of steroids for at least five days prior to registration.
- Patients must be greater than or equal to 18 years of age and less than or equal to age 70, and must have a life expectancy > 8 weeks
- Patients must be able to understand and sign the Informed Consent Document
- Must be willing to sign a durable power of attorney.
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- Patients of both genders must be willing to practice birth control for four months following treatment.
- Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
- Serology:
- Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
- Hematology WBC greater than or equal to 3000/mm(3) ANC greater than or equal to 1000/mm(3) without the support of filgrastim Platelet count greater than or equal to 100,000/mm(3) Hemoglobin greater than or equal to 8.0 g/dl (eligibility level for hemoglobin may be reached by transfusion)
- Chemistry:
- ALT/AST less than or equal to to 2.5 times the upper limit of normal Creatinine less than or equal to to 1.6 mg/dl Total bilirubin less than or equal to to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- Patients must be at least 4 weeks from radiation therapy. Additionally, patients must be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from procarbazine, 2 weeks from vincristine and 4 weeks from last bevacizumab administration. Patients must be at least 4 weeks from other cytotoxic therapies not listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen) including investigative agents. All toxicities from prior therapies should be resolved to CTCAE less than or equal to grade 1 (except for toxicities such as alopecia, or vitiligo).
Who cannot join
- A prior history of gliadel implantation in the past six months..
- Women who are currently pregnant or breast feeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- Active systemic infections, coagulation disorders or other major medical illnesses including those of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
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- History of coronary revascularization or ischemic symptoms.
- Clinically significant hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgery. History of prior intratumoral bleeding is not an exclusion criteria; patients who with history of prior intratumoral bleeding, however, need to undergo a non-contrast head CT to exclude acute bleeding.
- Other concomitant anti-cancer therapy except corticosteroids.
- Any patient known to have an LVEF less than or equal to 45%.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Cancer Institute
Xuhui, Shanghai Municipality, 200032
zonghai li, m.d, 86-21-64436601, zonghaili@163.com
Zonghai Li, M.D.
About this study
Official title: Genetically Modified T Cells in Treating Patients With Malignant Gliomas Overexpressing EGFR
The purpose of this study is to determine whether autologous T cells bearing chimeric antigen receptor that can specifically recognize EGFR overexpressed in tumor cells is safe and effective for patients with EGFR-overexpressing malignant glioma.
Read the detailed description
BACKGROUND:
- Patients with advanced gliomas have very limited treatment options. Epidermal Growth Factor Receptor (EGFR) is often amplified in patients with glioblastoma (GBM) and has been regarded a suitable target for GBM treatment.
The investigators have constructed lentiviral vector that contains a chimeric antigen receptor (CAR) that recognizes overexpressed EGFR in tumor cells but not EGFR in normal cells, which can be used to mediate genetic transfer of this CAR with high efficiency without the need to perform any selection.
OBJECTIVES:
Primary Objectives To evaluate the safety of the administration of anti-EGFR CAR engineered T lymphocytes in patients receiving the non-myeloablative conditioning regimen, and aldesleukin
Secondary objectives To determine whether the glioma will regress after the patients receive anti-EGFR CAR-engineered T lymphocytes and aldesleukin following a nonmyeloablative but lymphoid depleting preparative regimen.
ELIGIBILITY:
Histologically proven glioblastoma or glisarcoma overexpressing EGFR as determined by IHC, Western blot, FISH or RT-PCR.
Failed prior standard treatment with radiotherapy with or without chemotherapy. Cardiac, pulmonary and laboratory parameters within acceptable limits
DESIGN:
The study will be conducted using a Phase I design. Patients will receive a non-myeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumor reactive, CAR gene-transduced T cells, plus IV aldesleukin.
A total of 10 patients may be enrolled over a period of 1-2 years.
- Conditions
- Advanced Glioma
- Being tested
- anti-EGFR CAR T
- Keywords
- EGFR, CAR T cells, glioma
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-EGFR CAR TBiological
Also called CAR T cells targeting overexpressed EGFR in cancer cells
| Study group | Role | What they receive |
|---|---|---|
| anti-EGFR CAR T | Experimental | Not described Receives: Biological: anti-EGFR CAR T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events attributed to the administration of the anti-EGFR CAR T cells
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2015 (estimated)
- Study startDec 2014
- Primary completionDec 2015 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced GliomaStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02331693
- Sponsor's protocol ID
- RJ-20141110
- Status last verified
- Jan 2015
- First submitted
- 2 Jan 2015
- Last updated
- 6 Jan 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetically Modified T Cells in Treating Patients With Malignant Gliomas Overexpressing EGFR
- ClinicalTrials.gov ID
- NCT02331693
- Acronym / sponsor ID
- RJ-20141110
- Conditions
- Advanced Glioma
- Keywords
- EGFR, CAR T cells, glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 6 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether autologous T cells bearing chimeric antigen receptor that can specifically recognize EGFR overexpressed in tumor cells is safe and effective for patients with EGFR-overexpressing malignant glioma.
Detailed description
BACKGROUND:
- Patients with advanced gliomas have very limited treatment options. Epidermal Growth Factor Receptor (EGFR) is often amplified in patients with glioblastoma (GBM) and has been regarded a suitable target for GBM treatment.
The investigators have constructed lentiviral vector that contains a chimeric antigen receptor (CAR) that recognizes overexpressed EGFR in tumor cells but not EGFR in normal cells, which can be used to mediate genetic transfer of this CAR with high efficiency without the need to perform any selection.
OBJECTIVES:
Primary Objectives To evaluate the safety of the administration of anti-EGFR CAR engineered T lymphocytes in patients receiving the non-myeloablative conditioning regimen, and aldesleukin
Secondary objectives To determine whether the glioma will regress after the patients receive anti-EGFR CAR-engineered T lymphocytes and aldesleukin following a nonmyeloablative but lymphoid depleting preparative regimen.
ELIGIBILITY:
Histologically proven glioblastoma or glisarcoma overexpressing EGFR as determined by IHC, Western blot, FISH or RT-PCR.
Failed prior standard treatment with radiotherapy with or without chemotherapy. Cardiac, pulmonary and laboratory parameters within acceptable limits
DESIGN:
The study will be conducted using a Phase I design. Patients will receive a non-myeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumor reactive, CAR gene-transduced T cells, plus IV aldesleukin.
A total of 10 patients may be enrolled over a period of 1-2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti-EGFR CAR T | Experimental | Biological: anti-EGFR CAR T |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with histologically proven glioblastomas or gliosarcomas that overexpress EGFR as assessed by IHC, FISH, western blot or RT-PCR.
- Patients must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered NED). This includes recurrent GBM after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy.
- Patients must either not be receiving steroids, or be on a stable dose of steroids for at least five days prior to registration.
- Patients must be greater than or equal to 18 years of age and less than or equal to age 70, and must have a life expectancy > 8 weeks
- Patients must be able to understand and sign the Informed Consent Document
Key exclusion criteria (10 listed)
- A prior history of gliadel implantation in the past six months..
- Women who are currently pregnant or breast feeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- Active systemic infections, coagulation disorders or other major medical illnesses including those of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-EGFR CAR TAlso: CAR T cells targeting overexpressed EGFR in cancer cells | Biological | anti-EGFR CAR T |
Primary outcome
Adverse events attributed to the administration of the anti-EGFR CAR T cells
Time frame: Approximately 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing anti-EGFR CAR T in people with Advanced Glioma, run by RenJi Hospital at 1 site in China.
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 14 inclusion and 10 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 6 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Contact Zonghai Li, M.D (86-21-64436601, zonghaili@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events attributed to the administration of the anti-EGFR CAR T cells (time frame: Approximately 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jan 2015.