Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.


Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Biological: Anti-PD-L1 CSR T cells Drug: Cyclophosphamide Drug: Fludarabine Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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%).

Drug: Cyclophosphamide
250 mg/m^2, d1-3

Drug: Fludarabine
25mg/m^2, d1-3




Primary Outcome Measures :
  1. Number of Adverse Events related to CSR T cell infusion [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. 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).

  2. Overall Survival Rate [ Time Frame: 2 years ]
  3. Progression-free Survival Rate [ Time Frame: 6 months ]

Other Outcome Measures:
  1. Persistence of CSR T cells in patients [ Time Frame: 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Zhixiong Lin, MD +86-10-13905918963 lzx1967@sina.com

Locations
Layout table for location information
China
Sanbo Brain Hospital Capital Medical University Recruiting
Beijing, China, 100093
Contact: Zhixiong Lin, MD    +86-10-13905918963    lzx1967@sina.com   
Sponsors and Collaborators
Beijing Sanbo Brain Hospital
Marino Biotechnology Co., Ltd.

Layout table for additonal information
Responsible Party: Beijing Sanbo Brain Hospital
ClinicalTrials.gov Identifier: NCT02937844     History of Changes
Other Study ID Numbers: SBNK-2016-016-01
First Posted: October 19, 2016    Key Record Dates
Last Update Posted: October 19, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites