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PD-1 Antibody Expressing CAR T Cells for Mesothelin Positive Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03030001
Recruitment Status : Unknown
Verified January 2017 by Ningbo Cancer Hospital.
Recruitment status was:  Recruiting
First Posted : January 24, 2017
Last Update Posted : January 24, 2017
Information provided by (Responsible Party):
Ningbo Cancer Hospital

Brief Summary:
This is a single-arm, open-label, one center, dose escalation clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibody and chimeric antigen receptor targeting mesothelin in adult patients with mesothelin positive, recurrent or refractory malignant tumors.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Advanced Cancer Biological: PD-1 antibody expressing mesothelin specific CAR-T cells Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PD-1 Antibody Expressing Chimeric Antigen Receptor T Cells for Mesothelin Positive Advanced Malignancies
Estimated Study Start Date : February 15, 2017
Estimated Primary Completion Date : December 1, 2018
Estimated Study Completion Date : February 1, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: PD-1 antibody expressing CAR-T cells
PD-1 antibody expressing mesothelin specific CAR-T cells
Biological: PD-1 antibody expressing mesothelin specific CAR-T cells
Patients will receive an IV infusion of PD-1 antibody expressing mesothelin specific CAR engineered peripheral blood leukocyte. On day 21, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.

Primary Outcome Measures :
  1. Safety of infusion of autologous mesothelin specific CAR T cells [ Time Frame: 2 years ]
    Safety of infusion of autologous mesothelin specific CAR T cells with PD-1 antibody expressing in patients with relapsed or refractory advanced solid malignancies using the NCI CTCAE V4.0 criteria

Secondary Outcome Measures :
  1. the response evaluation criteria of solid tumor [ Time Frame: 2 years ]
    Defined as the overall response rate (ORR), the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on the response evaluation criteria in solid tumor version 1.1 (RECIST1.1).

  2. progression free survival [ Time Frame: 1 year ]
  3. overall survival [ Time Frame: 2 years ]

Other Outcome Measures:
  1. Change of life quality after treatment [ Time Frame: 2 years ]
  2. proliferation and persistence of mesothelin specific CAR T cells in patients after treatment [ Time Frame: 6 months ]
  3. expression of PD-1 antibody in patients after treatment [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 1. Relapsed or refractory advanced solid malignancies.
  • 2. Progressive disease and no response to current therapy.
  • 3. Patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred. And patients are willing to attend the clinical trial.
  • 4. Gender unlimited, age from 18 years to 80 years.
  • 5. Life expectancy≥6 months.
  • 6. ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
  • 7. Adequate venous access for apheresis, and no other contraindications for leukapheresis ; Peripheral venous access ;no contraindication of lymphocyte separation.
  • 8. IHC( immuno-histochemistry) result of tumor tissue: mesothelin positive for :frequency≥2,intensity≥2 +. The percentage of tumor cell nuclei stained (0, no staining; 1, ≤10%; 2, 10-50% and 3, >50%) and the staining intensity (ranging from 0 to 3+).
  • 9. Adequate hepatic function, renal function and bone marrow function:WBC≥3.0×109/L,PLT≥60×109/L,HGB≥85g/L,LY≥0.7×109/L; Alanine aminotransferase/Aspartate transaminase(ALT/AST) 2.5 times the upper limit of the normal value, total bilirubin(TBiL) 1times the upper limit of the normal value, Serum creatinine1.5 times the upper limit of the normal value.
  • 10. Willing and able to understand and sign the Informed Consent Document.
  • 11. Women of child-bearing age must have evidence of negative pregnancy test. Patients must be willing to practice birth control during and for four months following treatment.

Exclusion Criteria:

  • 1. Life expectancy6 months.
  • 2. Patients with uncontrolled active infection will be excluded.
  • 3. Patients with severe heart and lung dysfunction; uncontrolled hypertension, unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded; aberrant pulmonary function testing: with a forced expiratory volume (FEV) of <30%(predicted), diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) <30% and oxyhemoglobin saturation90% will be excluded.
  • 4. Patients with severe liver and kidney dysfunction or chronic diseases of important organs will be excluded.
  • 5. Patients with active autoimmune disease requiring immunosuppressive therapy will be excluded.
  • 6. Patients requiring corticosteroids (other than inhaled) will be excluded.
  • 7. Patients with other severe diseases or situations improper for the research will be excluded, including neurologic disease, mental disease, immune disease, metabolic disease, and contagious disease.
  • 8. Pregnant and/or lactating women will be excluded.
  • 9. Patients who have had other bio-therapy in the past 4 weeks.
  • 10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
  • 11. Patients with the subject suffering disease affects the understanding of informed consent or complying with study protocol will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030001

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Contact: Huajun Jin, PhD 86-13162257545 hj_jin@126.com

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China, Zhejiang
Ningbo No.5 Hospital (Ningbo Cancer Hospital) Recruiting
Ningbo, Zhejiang, China
Contact: Bi Wan    86-13310088259    biwang0218@126.com   
Contact: Jiangtao Wang    86-15888102792      
Sponsors and Collaborators
Ningbo Cancer Hospital
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Study Chair: Qijun Qian, PhD Shanghai Cell Therapy Engineering Research Institute
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Responsible Party: Ningbo Cancer Hospital
ClinicalTrials.gov Identifier: NCT03030001    
Other Study ID Numbers: H2017-01-P01
First Posted: January 24, 2017    Key Record Dates
Last Update Posted: January 24, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ningbo Cancer Hospital:
solid tumor
Additional relevant MeSH terms:
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Immunologic Factors
Physiological Effects of Drugs