Glioblastoma MultiformePhase 1NCT02937844
Pilot Study of Autologous Chimeric Switch Receptor Modified T Cells in Recurrent Glioblastoma Multiforme
A Phase 1 study testing Anti-PD-L1 CSR T cells, Cyclophosphamide and Fludarabine in people with Glioblastoma Multiforme, run by Beijing Sanbo Brain Hospital at 1 site in China.
Trial summary
CAR T cell immunotherapy has achieved great success in CD19+ B-cell malignancies. Whether this new generation of cell-based immunotherapy can be applied to solid tumors remain to be investigated, partly due to hostile immune-suppressive tumor microenvironment which favors tumor growth but not immune system. 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-PD-L1 CSR 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 PD-L1 positive confirmed by IHC;
- 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 Switch Receptor Engineered T Cells Redirected to PD-L1 in Patients With Recurrent Glioblastoma Multiforme
CAR T cell immunotherapy has achieved great success in CD19+ B-cell malignancies. Whether this new generation of cell-based immunotherapy can be applied to solid tumors remain to be investigated, partly due to hostile immune-suppressive tumor microenvironment which favors tumor growth but not immune system. Signaling pathway of programmed death 1 (PD-1) and its ligand PD-L1 plays an important role in suppressing immune response against tumors. PD-L1 is over-expressed in 88% of glioblastoma.
We constructed a chimeric switch receptor (CSR) containing the extracellular domain of PD1 fused to the transmembrane and cytoplasmic domain of the costimulatory molecule CD28. CSR modified T cells are able to recognize PD-L1-expressing tumor cells and transduce signals to activate T cells, which results in tumor killing. A truncated EGFR (tEGFR) which lacks of the ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the CSR vector and is used for in vivo tracking and ablation of CSR T cells when necessary. This pilot study is to determine the safety and efficacy of autologous CSR T cells in patients with recurrent glioblastoma.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Anti-PD-L1 CSR 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-PD-L1 CSR T cellsBiological
Prescribed CSR T cells are infused intravenously to patients in a three-day split-dose regimen（day0,10%; day1, 30%; day2, 60%）.
CyclophosphamideDrug
250 mg/m^2, d1-3
FludarabineDrug
25mg/m^2, d1-3
| Study group | Role | What they receive |
|---|---|---|
| Anti-PD-L1 CSR T cells | Experimental | Patients will receive lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide, followed by intravenous infusion of autologous anti- PD-L1 CSR 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-PD-L1 CSR T cells; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events related to CSR T cell infusion
Measured: 2 years
Secondary outcomes (3)
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: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02937844
- Sponsor's protocol ID
- SBNK-2016-016-01
- Status last verified
- Oct 2016
- First submitted
- 22 Jul 2016
- Last updated
- 19 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Efficacy Study of Autologous Chimeric Switch Receptor Engineered T Cells Redirected to PD-L1 in Patients With Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT02937844
- Acronym / sponsor ID
- SBNK-2016-016-01
- 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
- 19 Oct 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.
CAR T cell immunotherapy has achieved great success in CD19+ B-cell malignancies. Whether this new generation of cell-based immunotherapy can be applied to solid tumors remain to be investigated, partly due to hostile immune-suppressive tumor microenvironment which favors tumor growth but not immune system. Signaling pathway of programmed death 1 (PD-1) and its ligand PD-L1 plays an important role in suppressing immune response against tumors. PD-L1 is over-expressed in 88% of glioblastoma.
We constructed a chimeric switch receptor (CSR) containing the extracellular domain of PD1 fused to the transmembrane and cytoplasmic domain of the costimulatory molecule CD28. CSR modified T cells are able to recognize PD-L1-expressing tumor cells and transduce signals to activate T cells, which results in tumor killing. A truncated EGFR (tEGFR) which lacks of the ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the CSR vector and is used for in vivo tracking and ablation of CSR T cells when necessary. This pilot study is to determine the safety and efficacy of autologous CSR 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-PD-L1 CSR T cells | Experimental | Biological: Anti-PD-L1 CSR T cells, Drug: Cyclophosphamide, Drug: FludarabinePatients will receive lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide, followed by intravenous infusion of autologous anti- PD-L1 CSR 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 PD-L1 positive confirmed by IHC;
- 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-PD-L1 CSR T cellsPrescribed CSR T cells are infused intravenously to patients in a three-day split-dose regimen（day0,10%; day1, 30%; day2, 60%）. | Biological | Anti-PD-L1 CSR T cells |
| Cyclophosphamide250 mg/m^2, d1-3 | Drug | Anti-PD-L1 CSR T cells |
| Fludarabine25mg/m^2, d1-3 | Drug | Anti-PD-L1 CSR T cells |
Primary outcome
Number of Adverse Events related to CSR T cell infusion
Time frame: 2 years
3 secondary outcomes
Treatment Responses Rate
Time frame: 4 weeks
Overall Survival Rate
Time frame: 2 years
Progression-free Survival Rate
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
- Individual participant dataSharing planned: Undecided
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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-PD-L1 CSR 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 19 Oct 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?
Number of Adverse Events related to CSR T cell infusion (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 19 Oct 2016.