Clinical Trial: NCT02937844 - My Cancer Genome

NCT02937844

Description:

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.

Related Conditions:

Glioblastoma

Recruiting Status:

Unknown status

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02937844

Trial Eligibility

Document

Title

Brief Title: Pilot Study of Autologous Chimeric Switch Receptor Modified T Cells in Recurrent Glioblastoma Multiforme
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

Clinical Trial IDs

ORG STUDY ID: SBNK-2016-016-01
NCT ID: NCT02937844

Conditions

Glioblastoma Multiforme

Interventions

Drug	Synonyms	Arms
Anti-PD-L1 CSR T cells		Anti-PD-L1 CSR T cells
Cyclophosphamide		Anti-PD-L1 CSR T cells
Fludarabine		Anti-PD-L1 CSR T cells

Purpose

Trial Arms

Name	Type	Description	Interventions
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.	Anti-PD-L1 CSR T cells Cyclophosphamide Fludarabine

Eligibility Criteria

        Inclusion Criteria:

          1. abilities to understand and the willingness to provide written informed consent;

          2. patients are ≥ 18 and ≤ 70 years old;

          3. 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;

          4. Malignant cells are PD-L1 positive confirmed by IHC;

          5. karnofsky performance score (KPS) ≥ 60;

          6. life expectancy >3 months;

          7. 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;

          8. peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;

          9. satisfactory heart functions;

         10. patients must be willing to follow the orders of doctors;

         11. 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.

        Exclusion Criteria:

          1. a prior history of gliadel implantation 4 weeks before this study start or antibody
             based therapies;

          2. HIV positive;

          3. hepatitis B infection or hepatitis C infection;

          4. history of autoimmune disease, or other diseases require long-term administration of
             steroids or immunosuppressive therapies;

          5. history of allergic disease, or allergy to CAR T cells or study product excipients;

          6. patients already enrolled in other clinical study;

          7. patients, in the opinion of investigators, may not be eligible or not able to comply
             with the study.

Maximum Eligible Age:	70 Years
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Number of Adverse Events related to CSR T cell infusion
Time Frame:	2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:	Treatment Responses Rate
Time Frame:	4 weeks
Safety Issue:
Description:	Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease(SD), or progressive disease (PD).

Measure:	Overall Survival Rate
Time Frame:	2 years
Safety Issue:
Description:

Measure:	Progression-free Survival Rate
Time Frame:	6 months
Safety Issue:
Description:

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Unknown status
Lead Sponsor:	Beijing Sanbo Brain Hospital

Last Updated

October 19, 2016

Clinical Trials /

Pilot Study of Autologous Chimeric Switch Receptor Modified T Cells in Recurrent Glioblastoma Multiforme