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

NCT ID: NCT02844062

Last Updated: 2016-07-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2019-07-31

Brief Summary

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.

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

anti-EGFRvIII CAR T cells

Patients 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

Group Type: EXPERIMENTAL

anti-EGFRvIII CAR T cells

Intervention Type: BIOLOGICAL

CAR T cells are infused intravenously to patients in a three-day split-dose regimen（day0,10%; day1, 30%; day2, 60%）with a total targeted dose.

cyclophosphamide

Intervention Type: DRUG

250 mg/m\^2 d1-3

Fludarabine

Intervention Type: DRUG

25mg/m\^2 d1-3

Interventions

anti-EGFRvIII CAR T cells

CAR T cells are infused intravenously to patients in a three-day split-dose regimen（day0,10%; day1, 30%; day2, 60%）with a total targeted dose.

Intervention Type: BIOLOGICAL

cyclophosphamide

250 mg/m\^2 d1-3

Intervention Type: DRUG

Fludarabine

25mg/m\^2 d1-3

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marino Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Beijing Sanbo Brain Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhixiong Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Capital Medical University

Locations

Sanbo Brain Hospital Capital Medical University

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhixiong Lin, MD

Role: CONTACT

lzx1967@sina.com

+86-10-13905918963

Facility Contacts

Zhixiong Lin, MD

Role: primary

lzx1967@sina.com

+86-10-13905918963

Other Identifiers

SBNK-2016-015-01

Identifier Type: -

Identifier Source: org_study_id