Glioblastoma MultiformePhase 1NCT02844062
Pilot Study of Autologous Anti-EGFRvIII CAR T Cells in Recurrent Glioblastoma Multiforme
A Phase 1 study testing anti-EGFRvIII CAR T cells, cyclophosphamide and Fludarabine in people with Glioblastoma Multiforme, run by Beijing Sanbo Brain Hospital at 1 site in China.
Trial summary
Chimeric antigen receptor (CAR)-modified T cells can mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and are a promising therapy to treat glioblastoma, which is the most dangerous and aggressive form of brain cancer. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- anti-EGFRvIII CAR T cells, cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Jul 2016to Jul 2019
- 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
- abilities to understand and the willingness to provide written informed consent;
- patients are ≥ 18 and ≤ 70 years old;
- recurrent glioblastoma patients with measurable tumors. Patients have received standard care of medication, such as Gross Total Resection with concurrent Radio-chemotherapy (~54 - 60 Gy, TMZ). Patients must either not be receiving dexamethasone or receiving ≤ 4 mg/day at the time of leukopheresis;
- Malignant cells are EGFRvIII positive confirmed by IHC, quantitative PCR or sequencing;
- karnofsky performance score (KPS) ≥ 60;
- life expectancy >3 months;
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- satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN;
- peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
- satisfactory heart functions;
- patients must be willing to follow the orders of doctors;
- women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.
Who cannot join
- a prior history of gliadel implantation 4 weeks before this study start or antibody based therapies;
- HIV positive;
- hepatitis B infection or hepatitis C infection;
- history of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies;
- history of allergic disease, or allergy to CAR T cells or study product excipients;
- patients already enrolled in other clinical study;
- patients, in the opinion of investigators, may not be eligible or not able to comply with the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sanbo Brain Hospital Capital Medical University
Beijing, 100093
Zhixiong Lin, MD, +86-10-13905918963, lzx1967@sina.com
About this study
Official title: A Safety and Efficacy Study of Autologous Chimeric Antigen Receptor Engineered T Cells Redirected to EGFRvIII in Patients With Recurrent Glioblastoma Multiforme
Chimeric antigen receptor (CAR)-modified T cells can mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and are a promising therapy to treat glioblastoma, which is the most dangerous and aggressive form of brain cancer. EGFRvIII mutation (epidermal growth factor receptor variant III, EGFRvIII) is the results of tumor specific gene rearrangement naturally happened in about 30% of glioblastoma patients and produces a mutated protein with neo-antigen that is tumor specific and is not expressed in normal human tissues. Therefore, EGFRvIII is an attractive target for CAR T cell therapy. We have constructed a lentiviral vector that contains a chimeric antigen receptor that recognizes the EGFRvIII tumor antigen. A truncated EGFR (tEGFR) which lacks of the ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the CAR vector and is used for in vivo tracking and ablation of CAR T cells in necessary. This pilot study is to determine the safety and efficacy of autologous anti-EGFRvIII CAR T cells in patients with recurrent glioblastoma.
- Conditions
- Glioblastoma Multiforme
- Being tested
- anti-EGFRvIII CAR T cells, cyclophosphamide, Fludarabine
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-EGFRvIII CAR T cellsBiological
CAR T cells are infused intravenously to patients in a three-day split-dose regimen（day0,10%; day1, 30%; day2, 60%）with a total targeted dose.
cyclophosphamideDrug
250 mg/m^2 d1-3
FludarabineDrug
25mg/m^2 d1-3
| Study group | Role | What they receive |
|---|---|---|
| anti-EGFRvIII CAR T cells | Experimental | Patients will receive lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide, followed by intravenous infusion of autologous anti-EGFRvIII CAR T cells. A standard 3+3 escalation approach will be used to obtain the safe dosage of CAR T cells. The tested CAR T cell dosage ranges from 5×10^4 /kg to 1×10^7 /kg Receives: Biological: anti-EGFRvIII CAR T cells; Drug: cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of infusion of autologous anti-EGFRvIII CAR T cells with cyclophosphamide and fludarabine as lymphodepleting chemotherapy in patients with recurrent glioblastoma using the NCI CTCAE V4.0 criteria.
incidents of treatment related adverse events as assessed by CTCAE V4.0.
Measured: 2 years
Secondary outcomes (4)
Treatment Responses Rate
defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).
Measured: 4 weeks
Overall Survival Rate
Measured: 2 years
Progression-free Survival Rate
Measured: 2 years
Persistence of CAR T cells in patients
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionJul 2018 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Sanbo Brain Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Marino Biotechnology Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Zhixiong Lin, MD, Principal investigator, Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02844062
- Sponsor's protocol ID
- SBNK-2016-015-01
- Status last verified
- Jul 2016
- First submitted
- 22 Jul 2016
- Last updated
- 26 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Efficacy Study of Autologous Chimeric Antigen Receptor Engineered T Cells Redirected to EGFRvIII in Patients With Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT02844062
- Acronym / sponsor ID
- SBNK-2016-015-01
- Conditions
- Glioblastoma Multiforme
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Beijing Sanbo Brain HospitalUniversity, hospital or other
- Collaborators
- Marino Biotechnology Co., Ltd.
- Study start
- Jul 2016
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 26 Jul 2016 (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.
Chimeric antigen receptor (CAR)-modified T cells can mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and are a promising therapy to treat glioblastoma, which is the most dangerous and aggressive form of brain cancer. EGFRvIII mutation (epidermal growth factor receptor variant III, EGFRvIII) is the results of tumor specific gene rearrangement naturally happened in about 30% of glioblastoma patients and produces a mutated protein with neo-antigen that is tumor specific and is not expressed in normal human tissues. Therefore, EGFRvIII is an attractive target for CAR T cell therapy. We have constructed a lentiviral vector that contains a chimeric antigen receptor that recognizes the EGFRvIII tumor antigen. A truncated EGFR (tEGFR) which lacks of the ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the CAR vector and is used for in vivo tracking and ablation of CAR T cells in necessary. This pilot study is to determine the safety and efficacy of autologous anti-EGFRvIII CAR T cells in patients with recurrent glioblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti-EGFRvIII CAR T cells | Experimental | Biological: anti-EGFRvIII CAR T cells, Drug: cyclophosphamide, Drug: FludarabinePatients will receive lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide, followed by intravenous infusion of autologous anti-EGFRvIII CAR T cells. A standard 3+3 escalation approach will be used to obtain the safe dosage of CAR T cells. The tested CAR T cell dosage ranges from 5×10^4 /kg to 1×10^7 /kg |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- abilities to understand and the willingness to provide written informed consent;
- patients are ≥ 18 and ≤ 70 years old;
- recurrent glioblastoma patients with measurable tumors. Patients have received standard care of medication, such as Gross Total Resection with concurrent Radio-chemotherapy (~54 - 60 Gy, TMZ). Patients must either not be receiving dexamethasone or receiving ≤ 4 mg/day at the time of leukopheresis;
- Malignant cells are EGFRvIII positive confirmed by IHC, quantitative PCR or sequencing;
- karnofsky performance score (KPS) ≥ 60;
Key exclusion criteria (7 listed)
- a prior history of gliadel implantation 4 weeks before this study start or antibody based therapies;
- HIV positive;
- hepatitis B infection or hepatitis C infection;
- history of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies;
- history of allergic disease, or allergy to CAR T cells or study product excipients;
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-EGFRvIII CAR T cellsCAR T cells are infused intravenously to patients in a three-day split-dose regimen（day0,10%; day1, 30%; day2, 60%）with a total targeted dose. | Biological | anti-EGFRvIII CAR T cells |
| cyclophosphamide250 mg/m^2 d1-3 | Drug | anti-EGFRvIII CAR T cells |
| Fludarabine25mg/m^2 d1-3 | Drug | anti-EGFRvIII CAR T cells |
Primary outcome
Safety of infusion of autologous anti-EGFRvIII CAR T cells with cyclophosphamide and fludarabine as lymphodepleting chemotherapy in patients with recurrent glioblastoma using the NCI CTCAE V4.0 criteria.
Time frame: 2 years
incidents of treatment related adverse events as assessed by CTCAE V4.0.
4 secondary outcomes
Treatment Responses Rate
Time frame: 4 weeks
Overall Survival Rate
Time frame: 2 years
Progression-free Survival Rate
Time frame: 2 years
Persistence of CAR T cells in patients
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2016.
- Individual participant dataSharing planned: Yes
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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.
Zhixiong Lin, MD principal investigator
Capital Medical University
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-EGFRvIII CAR T cells, cyclophosphamide and Fludarabine in people with Glioblastoma Multiforme, run by Beijing Sanbo Brain 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 11 inclusion and 7 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 26 Jul 2016. 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 Zhixiong Lin, MD (+86-10-13905918963, lzx1967@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of infusion of autologous anti-EGFRvIII CAR T cells with cyclophosphamide and fludarabine as lymphodepleting chemotherapy in patients with recurrent glioblastoma using the NCI CTCAE V4.0 criteria. (time frame: 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 26 Jul 2016.