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

Glioblastoma Multiforme Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT02844062
• Other study ID #: SBNK-2016-015-01
• Status: Recruiting
• Phase: Phase 1
• First received: July 22, 2016
• Last updated: July 22, 2016
• Start date: July 2016
• Est. completion date: July 2019

Study information

• Verified date: July 2016
• Source: Beijing Sanbo Brain Hospital
• Contact: Zhixiong Lin, MD
• Phone: +86-10-13905918963
• Email: lzx1967[@]sina.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 2019
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Biological:
• 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.

Drug:
• cyclophosphamide
250 mg/m^2 d1-3
• Fludarabine
25mg/m^2 d1-3

Locations

Country	Name	City	State
China	Sanbo Brain Hospital Capital Medical University	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Sanbo Brain Hospital	Marino Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proliferation of CAR T cells in patients	CAR T cell proliferation in patients is monitored by flow or qPCR	2 years	No
Primary	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.	incidents of treatment related adverse events as assessed by CTCAE V4.0.	2 years	Yes
Secondary	Treatment Responses Rate	defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).	4 weeks	No
Secondary	Overall Survival Rate		2 years	No
Secondary	Progression-free Survival Rate		2 years	No
Secondary	Persistence of CAR T cells in patients		2 years	No