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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02844062
Recruitment Status : Unknown
Verified July 2016 by Beijing Sanbo Brain Hospital.
Recruitment status was:  Recruiting
First Posted : July 26, 2016
Last Update Posted : July 26, 2016
Sponsor:
Collaborator:
Marino Biotechnology Co., Ltd.
Information provided by (Responsible Party):
Beijing Sanbo Brain Hospital

Tracking Information
First Submitted Date  ICMJE July 22, 2016
First Posted Date  ICMJE July 26, 2016
Last Update Posted Date July 26, 2016
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE 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  ICMJE Pilot Study of Autologous Anti-EGFRvIII CAR T Cells in Recurrent Glioblastoma Multiforme
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE
  • 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  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: July 22, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2019
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02844062
Other Study ID Numbers  ICMJE SBNK-2016-015-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Beijing Sanbo Brain Hospital
Study Sponsor  ICMJE Beijing Sanbo Brain Hospital
Collaborators  ICMJE Marino Biotechnology Co., Ltd.
Investigators  ICMJE
Principal Investigator: Zhixiong Lin, MD Sanbo Brain Hospital Capital Medical University
PRS Account Beijing Sanbo Brain Hospital
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP