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CART-meso in Mesothelin Expressing Cancers

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: NCT02159716
Recruitment Status : Completed
First Posted : June 10, 2014
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE June 6, 2014
First Posted Date  ICMJE June 10, 2014
Last Update Posted Date February 26, 2019
Study Start Date  ICMJE June 2014
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2014)
Number of Adverse Events [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CART-meso in Mesothelin Expressing Cancers
Official Title  ICMJE Phase I Study of Chimeric Antigen Receptor Modified T Cells in Patients With Mesothelin Expressing Cancers
Brief Summary Phase I study to establish safety and feasibility of intravenously administered lentiviral transduced CART-meso cells administered with and without cyclophosphamide in a 3+3 dose escalation design in patients with metastatic pancreatic cancer, serous epithelial ovarian cancer, or pleural mesothelioma. Dose: 1-3xE7 /mE2 (Cohort 1 and 2) and 1-3xE8 /mE2 (Cohort 3 and 4 ) CAR+ T cells by intravenous route. In the event of 2 DLTs at each dose level, we will dose deescalate by 10-fold.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Pancreatic (Ductal) Adenocarcinoma
  • Epithelial Ovarian Cancer
  • Malignant Epithelial Pleural Mesothelioma
Intervention  ICMJE Biological: CART-meso
CART-meso are autologous T cells lentivirally transduced with chimeric anti-mesothelin immunoreceptor SS1 fused to the 4-1BB and CD3ζ signaling domains.
Study Arms  ICMJE
  • Experimental: Metastatic Pancreatic (ductal) adenocarcinoma (PDA)
    Intervention: Biological: CART-meso
  • Experimental: Serious Epithelial Ovarian Cancer
    Intervention: Biological: CART-meso
  • Experimental: Malignant Epithelial Pleaural Mesothelioma
    Intervention: Biological: CART-meso
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 Completed
Actual Enrollment  ICMJE
 (submitted: September 15, 2016)
19
Original Estimated Enrollment  ICMJE
 (submitted: June 9, 2014)
24
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed cancer (one of the following):

    • Metastatic pancreatic adenocarcinoma.
    • Persistent or recurrent serous epithelial ovarian cancer or primary peritoneal carcinoma
    • Malignant pleural mesothelioma (histologically confirmed epithelial)
  • Failure of at least one prior standard of care chemotherapy for advanced stage disease.
  • Subjects must have measureable disease as defined by RECIST 1.1 criteria or modified RECIST criteria.
  • Patients > 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy > 3 months.
  • 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.

  • 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.
  • Ability to understand and the willingness to provide written informed consent.
  • 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

  • Sarcomatoid MPM histology which is known in the literature to not express mesothelin; biphasic MPM is also excluded.
  • 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. This refers to non-commercially approved investigational drugs different than those used in this protocol.
  • Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion of CART-meso cells.
  • 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
  • HIV, HCV, or HBV infections
  • 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.
  • Patients with ongoing or active infection.
  • 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.
  • Patients requiring supplemental oxygen therapy.
  • Prior therapy with gene modified cells.
  • Previous experimental therapy with SS1 moiety, murine or chimeric antibodies (human and humanized antibodies are allowed).
  • History of allergy to murine proteins
  • History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
  • 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.
  • Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to enrollment is acceptable.
  • 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 and older   (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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02159716
Other Study ID Numbers  ICMJE UPCC 31213, 819826
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew Haas, MD Ambramson Cancer Center of the University of Pennsylvania
Principal Investigator: Andrew Haas, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date February 2019

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