Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors.

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03545815
Recruitment Status : Recruiting
First Posted : June 4, 2018
Last Update Posted : June 4, 2018
Sponsor:
Information provided by (Responsible Party):
Han weidong, Chinese PLA General Hospital

Tracking Information
First Submitted Date  ICMJE May 23, 2018
First Posted Date  ICMJE June 4, 2018
Last Update Posted Date June 4, 2018
Actual Study Start Date  ICMJE March 1, 2018
Estimated Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
study of related adverse events [ Time Frame: 24 weeks ]
Grade 3 signs/symptoms, toxicities and clinical
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
clinical responses to anti-mesothelin cell infusions [ Time Frame: 24 weeks ]
Disease control rate(DCR)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors.
Official Title  ICMJE Phase I Study to Evaluate Treatment of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Chimeric Antigen Receptor (CAR) T Cells in Patients With Mesothelin Positive Multiple Solid Tumors.
Brief Summary Multiple solid tumors have positive targets of mesothelin expressed on the surfaces of the tumor cells, we use the technique of CRISPR-Cas9 to knocked out the PD-1 and TCR of chimeric antigen receptor (CAR) T cells to effect the immuno-microenvironment around tumors.
Detailed Description
  1. To evaluate the feasibility and safety of CRISPR-Cas9 mediated PD-1 and TCR gene-knocked out chimeric antigen receptor (CAR) T cells in patients with mesothelin positive multiple solid tumors.
  2. To evaluate the duration of in vivo persistence of transferred CAR-T cells.
  3. To observe and measure anti-tumor responses for patients with detectable mesothelin positive tumor lesions.
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 Solid Tumor, Adult
Intervention  ICMJE Biological: anti-mesothelin CAR-T cells
Cells will be infused 1 day after the completion of conditioning regimen.
Study Arms  ICMJE Experimental: anti-mesothelin CAR-T cells

Patients receive mesothelin-directed CAR-T cells infusion with dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de- escalation.

Patients receive anti-mesothelin-CAR T cells on days 0, 1, 2 in the absence of disease progression or unacceptable toxicity.

Intervention: Biological: anti-mesothelin CAR-T cells
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 23, 2018)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2019
Estimated Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed with mesothelin positive multiple solid tumors.
  2. Failure of at least one prior standard of care chemotherapy for advanced stage disease.
  3. Subjects must have measureable disease as defined by RECIST 1.1 criteria or modified RECIST criteria.
  4. Patients > 18 years of age.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
  6. Life expectancy > 12 weeks.
  7. Satisfactory organ and bone marrow function as defined by the following (of note, the minimal blood counts should be in the absence of transfusion or cytokine support):

    i. Absolute neutrophil count > 1,000/μl ii. Platelets >75,000/μl iii. Hemoglobin > 9 g/dL iv. Bilirubin < 2.0x the institutional normal upper limit unless secondary to bile duct obstruction by tumor v. Creatinine < 1.5x the institutional normal upper limit vi. Albumin ≥2 vii. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5x the institutional normal upper limit viii. Cardiac ejection fraction of >55% as measured by resting echocardiogram, with no significant pericardial effusion.

  8. Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT < 1.2 time the upper limit of normal unless the patient is therapeutically anti-coagulated for history of cancer-related thrombosis and has stable coagulation parameters.
  9. Ability to understand and the willingness to provide written informed consent.
  10. Male and Female subjects of reproductive potential agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) and abstain from other methods of conception during the study and for 6 months following the study cell infusion or proof of sterility.

Exclusion Criteria

  1. Sarcomatoid MPM histology which is known in the literature to not express mesothelin; biphasic MPM is also excluded.
  2. This refers to non-commercially approved investigational drugs different than those used in this protocol.Participated in any other trial in which receipt of an investigational study drug occurred within 28 days prior to enrollment and anticipated treatment with another investigational product while on study.
  3. Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion of CART-meso cells.
  4. Active invasive cancer other than the one of the three cancers in this study. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level < 1.0) are not excluded.CART-meso in mesothelin expressing cancers
  5. HIV, HCV, or HBV infections
  6. Active autoimmune disease (including but not limited to: systemic lupus erythromatosis, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within the past 4 weeks, with exception of thyroid replacement.
  7. Patients with ongoing or active infection.
  8. Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (<10mg equivalent of prednisone) for chronic respiratory conditions.
  9. Patients requiring supplemental oxygen therapy.
  10. Prior therapy with gene modified cells.
  11. Previous experimental therapy with SS1 moiety, murine or chimeric antibodies (human and humanized antibodies are allowed).
  12. History of allergy to murine proteins
  13. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
  14. Any clinically significant pericardial effusion; CHF (NY Heart Association Grade II-IV) or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist.
  15. Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to enrollment is acceptable.
  16. Pregnant or breastfeeding women. Female study participants of reproductive potential must have a negative urine pregnancy test of enrollment. A serum pregnancy test will be performed within 2 weeks before infusion.
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: Wweidong Han, Dr. 86-10-13651392893 hanwdrsw@sina.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03545815
Other Study ID Numbers  ICMJE CHN-PLAGH-BT-028
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Han weidong, Chinese PLA General Hospital
Study Sponsor  ICMJE Chinese PLA General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chinese PLA General Hospital
Verification Date March 2018

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