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

Primary Purpose

Glioblastoma Multiforme

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

anti-EGFRvIII CAR T cells

cyclophosphamide

Fludarabine

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Sanbo Brain Hospital Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-EGFRvIII CAR T cells

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Treatment Responses Rate

defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

Overall Survival Rate

Progression-free Survival Rate

Persistence of CAR T cells in patients

Full Information

NCT ID

NCT02844062

First Posted

July 22, 2016

Last Updated

July 22, 2016

Sponsor

Beijing Sanbo Brain Hospital

Collaborators

Marino Biotechnology Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02844062

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Unknown status

Study Start Date

July 2016 (undefined)

Primary Completion Date

July 2018 (Anticipated)

Study Completion Date

July 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Beijing Sanbo Brain Hospital

Collaborators

Marino Biotechnology Co., Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

anti-EGFRvIII CAR T cells

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

anti-EGFRvIII CAR T cells

Intervention Description

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

Drug

Intervention Name(s)

cyclophosphamide

Intervention Description

250 mg/m^2 d1-3

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

25mg/m^2 d1-3

Primary Outcome Measure Information:

Title

Description

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

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Treatment Responses Rate

Description

defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

Time Frame

4 weeks

Title

Overall Survival Rate

Time Frame

2 years

Title

Progression-free Survival Rate

Time Frame

2 years

Title

Persistence of CAR T cells in patients

Time Frame

2 years

Other Pre-specified Outcome Measures:

Title

Proliferation of CAR T cells in patients

Description

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

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhixiong Lin, MD

Phone

+86-10-13905918963

lzx1967@sina.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhixiong Lin, MD

Organizational Affiliation

Capital Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sanbo Brain Hospital Capital Medical University

City

Beijing

ZIP/Postal Code

100093

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhixiong Lin, MD

Phone

+86-10-13905918963

lzx1967@sina.com

12. IPD Sharing Statement

Plan to Share IPD

Yes

Learn more about this trial

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

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