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

• ClinicalTrials.gov Identifier: NCT02844062
• Recruitment Status: Unknown
• First Posted: July 26, 2016
• Last Update Posted: July 26, 2016
• Sponsor: Beijing Sanbo Brain Hospital
• Collaborator: Marino Biotechnology Co., Ltd.
• Information provided by (Responsible Party): Beijing Sanbo Brain Hospital

Tracking Information

• First Submitted Date: July 22, 2016
• First Posted Date: July 26, 2016
• Last Update Posted Date: July 26, 2016
• Study Start Date: July 2016
• Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 22, 2016)

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 ]

incidents of treatment related adverse events as assessed by CTCAE V4.0.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 22, 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: 2 years ]
• Persistence of CAR T cells in patients [ Time Frame: 2 years ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: July 22, 2016)

Proliferation of CAR T cells in patients [ Time Frame: 2 years ]

CAR T cell proliferation in patients is monitored by flow or qPCR

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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
• Drug: Fludarabine
  25mg/m^2 d1-3

Study Arms

Experimental: 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

Interventions:

• Biological: anti-EGFRvIII CAR T cells
• Drug: cyclophosphamide
• Drug: Fludarabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 22, 2016): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2019
• Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02844062
• Other Study ID Numbers: SBNK-2016-015-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Beijing Sanbo Brain Hospital
• Study Sponsor: Beijing Sanbo Brain Hospital
• Collaborators: Marino Biotechnology Co., Ltd.

Investigators

• Principal Investigator: Zhixiong Lin, MD; Sanbo Brain Hospital Capital Medical University

• PRS Account: Beijing Sanbo Brain Hospital
• Verification Date: July 2016