Clinical Trials /

Pilot Study of Autologous Anti-EGFRvIII CAR T Cells in Recurrent Glioblastoma Multiforme

NCT02844062

Description:

Chimeric antigen receptor (CAR)-modified T cells can mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and are a promising therapy to treat glioblastoma, which is the most dangerous and aggressive form of brain cancer. EGFRvIII mutation (epidermal growth factor receptor variant III, EGFRvIII) is the results of tumor specific gene rearrangement naturally happened in about 30% of glioblastoma patients and produces a mutated protein with neo-antigen that is tumor specific and is not expressed in normal human tissues. Therefore, EGFRvIII is an attractive target for CAR T cell therapy. We have constructed a lentiviral vector that contains a chimeric antigen receptor that recognizes the EGFRvIII tumor antigen. A truncated EGFR (tEGFR) which lacks of the ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the CAR vector and is used for in vivo tracking and ablation of CAR T cells in necessary. This pilot study is to determine the safety and efficacy of autologous anti-EGFRvIII CAR T cells in patients with recurrent glioblastoma.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of Autologous Anti-EGFRvIII CAR T Cells in Recurrent Glioblastoma Multiforme
  • Official Title: A Safety and Efficacy Study of Autologous Chimeric Antigen Receptor Engineered T Cells Redirected to EGFRvIII in Patients With Recurrent Glioblastoma Multiforme

Clinical Trial IDs

  • ORG STUDY ID: SBNK-2016-015-01
  • NCT ID: NCT02844062

Conditions

  • Glioblastoma Multiforme

Interventions

DrugSynonymsArms
anti-EGFRvIII CAR T cellsanti-EGFRvIII CAR T cells
cyclophosphamideanti-EGFRvIII CAR T cells
Fludarabineanti-EGFRvIII CAR T cells

Purpose

Chimeric antigen receptor (CAR)-modified T cells can mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and are a promising therapy to treat glioblastoma, which is the most dangerous and aggressive form of brain cancer. EGFRvIII mutation (epidermal growth factor receptor variant III, EGFRvIII) is the results of tumor specific gene rearrangement naturally happened in about 30% of glioblastoma patients and produces a mutated protein with neo-antigen that is tumor specific and is not expressed in normal human tissues. Therefore, EGFRvIII is an attractive target for CAR T cell therapy. We have constructed a lentiviral vector that contains a chimeric antigen receptor that recognizes the EGFRvIII tumor antigen. A truncated EGFR (tEGFR) which lacks of the ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the CAR vector and is used for in vivo tracking and ablation of CAR T cells in necessary. This pilot study is to determine the safety and efficacy of autologous anti-EGFRvIII CAR T cells in patients with recurrent glioblastoma.

Trial Arms

NameTypeDescriptionInterventions
anti-EGFRvIII CAR T cellsExperimentalPatients will receive lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide, followed by intravenous infusion of autologous anti-EGFRvIII CAR 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
  • 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 EGFRvIII positive confirmed by IHC, quantitative PCR or
             sequencing;

          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:Safety of infusion of autologous anti-EGFRvIII CAR T cells with cyclophosphamide and fludarabine as lymphodepleting chemotherapy in patients with recurrent glioblastoma using the NCI CTCAE V4.0 criteria.
Time Frame:2 years
Safety Issue:
Description:incidents of treatment related adverse events as assessed by CTCAE V4.0.

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:2 years
Safety Issue:
Description:
Measure:Persistence of CAR T cells in patients
Time Frame:2 years
Safety Issue:
Description:

Details

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

Last Updated

July 22, 2016