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

NCT02844062 | Unknown Phase 1 DMC

• 1 other identifier: SBNK-2016-015-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Treatment Responses Rate

  4 weeks

• Overall Survival Rate

  2 years

• Progression-free Survival Rate

  2 years

• Persistence of CAR T cells in patients

  2 years

Other Outcomes (1)

• Proliferation of CAR T cells in patients

  2 years

Study Arms (1)

anti-EGFRvIII CAR T cells

EXPERIMENTAL

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

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

Interventions

anti-EGFRvIII CAR T cells 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.

anti-EGFRvIII CAR T cells

cyclophosphamide DRUG

250 mg/m\^2 d1-3

anti-EGFRvIII CAR T cells

Fludarabine DRUG

25mg/m\^2 d1-3

anti-EGFRvIII CAR T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• abilities to understand and the willingness to provide written informed consent;
• patients are ≥ 18 and ≤ 70 years old;
• 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;
• Malignant cells are EGFRvIII positive confirmed by IHC, quantitative PCR or sequencing;
• karnofsky performance score (KPS) ≥ 60;
• life expectancy \>3 months;
• 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;
• peripheral blood absolute lymphocyte count must be above 0.8×10\^9/L;
• satisfactory heart functions;
• patients must be willing to follow the orders of doctors;
• 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.

You may not qualify if:

• a prior history of gliadel implantation 4 weeks before this study start or antibody based therapies;
• HIV positive;
• hepatitis B infection or hepatitis C infection;
• history of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies;
• history of allergic disease, or allergy to CAR T cells or study product excipients;
• patients already enrolled in other clinical study;
• patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Sponsors & Collaborators

• Beijing Sanbo Brain Hospital: lead
• Marino Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Sanbo Brain Hospital Capital Medical University

Beijing, 100093, China

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Zhixiong Lin, MD

  Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhixiong Lin, MD

CONTACT

+86-10-13905918963; lzx1967@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2016
• First Posted: July 26, 2016
• Study Start: July 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2019
• Last Updated: July 26, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)