Pilot Study of Autologous Chimeric Switch Receptor Modified T Cells in Recurrent Glioblastoma Multiforme
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|ClinicalTrials.gov Identifier: NCT02937844|
Recruitment Status : Unknown
Verified October 2016 by Beijing Sanbo Brain Hospital.
Recruitment status was: Recruiting
First Posted : October 19, 2016
Last Update Posted : October 19, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Biological: Anti-PD-L1 CSR T cells Drug: Cyclophosphamide Drug: Fludarabine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||July 2016|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||July 2019|
Experimental: Anti-PD-L1 CSR T cells
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.
Biological: Anti-PD-L1 CSR T cells
Prescribed CSR T cells are infused intravenously to patients in a three-day split-dose regimen（day0,10%; day1, 30%; day2, 60%）.
250 mg/m^2, d1-3
- Number of Adverse Events related to CSR T cell infusion [ Time Frame: 2 years ]
- Treatment Responses Rate [ Time Frame: 4 weeks ]Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease(SD), or progressive disease (PD).
- Overall Survival Rate [ Time Frame: 2 years ]
- Progression-free Survival Rate [ Time Frame: 6 months ]
- Persistence of CSR T cells in patients [ Time Frame: 12 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02937844
|Contact: Zhixiong Lin, MDfirstname.lastname@example.org|
|Sanbo Brain Hospital Capital Medical University||Recruiting|
|Beijing, China, 100093|
|Contact: Zhixiong Lin, MD +86-10-13905918963 email@example.com|