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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Collaborator:
Marino Biotechnology Co., Ltd.
Information provided by (Responsible Party):
Beijing Sanbo Brain Hospital

Tracking Information
First Submitted Date  ICMJE July 22, 2016
First Posted Date  ICMJE October 19, 2016
Last Update Posted Date October 19, 2016
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2016)
Number of Adverse Events related to CSR T cell infusion [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 17, 2016)
Persistence of CSR T cells in patients [ Time Frame: 12 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Autologous Chimeric Switch Receptor Modified T Cells in Recurrent Glioblastoma Multiforme
Official Title  ICMJE A Safety and Efficacy Study of Autologous Chimeric Switch Receptor Engineered T Cells Redirected to PD-L1 in Patients With Recurrent Glioblastoma Multiforme
Brief 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. 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE
  • 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%).
  • Drug: Cyclophosphamide
    250 mg/m^2, d1-3
  • Drug: Fludarabine
    25mg/m^2, d1-3
Study Arms  ICMJE 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.
Interventions:
  • Biological: Anti-PD-L1 CSR T cells
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 17, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2019
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02937844
Other Study ID Numbers  ICMJE SBNK-2016-016-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Beijing Sanbo Brain Hospital
Study Sponsor  ICMJE Beijing Sanbo Brain Hospital
Collaborators  ICMJE Marino Biotechnology Co., Ltd.
Investigators  ICMJE Not Provided
PRS Account Beijing Sanbo Brain Hospital
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP