Clinical Trials /

CAR T Cell Immunotherapy for Pancreatic Cancer

NCT03323944

Description:

This study will evaluate an immunotherapy approach to pancreatic cancer, where subjects' own immune cells are engineered to treat their cancer. Specifically, the study seeks to determine the safety and feasibility of intravenous administration of transduced huCART-meso cells in subjects with histologically confirmed unresectable or metastatic pancreatic adenocarcinoma both with and without cyclophosphamide as lymphodepleting chemotherapy.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CAR T Cell Immunotherapy for Pancreatic Cancer
  • Official Title: Phase I Study of Human Chimeric Antigen Receptor Modified T Cells (CAR T Cells) in Patients With Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 827664
  • NCT ID: NCT03323944

Conditions

  • Pancreatic Cancer
  • Cancer of the Pancreas

Interventions

DrugSynonymsArms
huCART-meso cellsCohort 1: huCART-meso cells only

Purpose

This study will evaluate an immunotherapy approach to pancreatic cancer, where patients' own immune cells are engineered to treat their cancer. Specifically, the study will determine the safety and feasibility of intravenous administration of transduced huCART-meso cells in patients with histologically confirmed unresectable or metastatic pancreatic adenocarcinoma, with and without cyclophosphamide as lymphodepleting chemotherapy.

Detailed Description

      This is a Phase I study evaluating the safety and feasibility of lentiviral transduced
      huCART-meso cells in 3 cohorts with and without cyclophosphamide in a 3+3 dose escalation
      design.

      The trial will begin in Cohort 1 and progress to Cohorts 2 and 3 chronologically, depending
      upon dose limiting toxicity (DLT) assessment. Subjects will be enrolled serially, but
      infusions will be staggered to allow assessment of DLTs for determination of cohort
      progression, expansion, or dose de-escalation.

      Cohort 1 subjects (N=3-6) will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced
      huCART-meso cells on day 0 without any conditioning chemotherapeutic regimen.

      Cohort 2 subjects (N=3-6) will receive a single dose of 1-3x10^8 /m^2 lentiviral transduced
      huCART-meso cells on day 0 without any conditioning chemotherapeutic regimen.

      Cohort 3 subjects (N=3-6) will receive a single dose of 1-3x10^8 /m^2 lentiviral transduced
      huCART-meso cells on day 0, following a flat dose of 1 gram/m^2 of cyclophosphamide
      administered 2-4 days prior to the huCART-meso cells (day -4 to day -2).

      The maximum tolerated dose (MTD) is defined as the dose level at which 0 or 1 subject among 6
      subjects in one cohort experiences a DLT within the dose range specified.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: huCART-meso cells onlyExperimentalSubjects will receive a single dose of 1-3x10^7/m^2 lentiviral transduced huCART-meso cells without any conditioning chemotherapeutic regimen.
    Cohort 2: huCART-meso cells onlyExperimentalSubjects will receive a single dose of 1-3x10^8/m^2 lentiviral transduced huCART-meso cells without any conditioning chemotherapeutic regimen.
      Cohort 3: huCART-meso cells after chemoExperimentalSubjects will receive a single dose of 1-3x10^8/m^2 lentiviral transduced huCART-meso cells following a flat dose of 1 gram/m^2 cyclophosphamide as lymphodepleting chemotherapy.

        Eligibility Criteria

                Inclusion Criteria:
        
                  1. Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma
        
                  2. Confirmation of tumor mesothelin expression (≥50% of tumor cells)
        
                  3. Failure of at least one prior standard of care chemotherapy for advanced stage
                     disease.
        
                  4. Subjects must have measureable disease as defined by RECIST 1.1 criteria.
        
                  5. Patients > 18 years of age.
        
                  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
        
                  7. Satisfactory organ and bone marrow function as defined by the following:
        
                     (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; (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 >40% as measured by resting
                     echocardiogram, with no clinically 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. Provides written informed consent.
        
                 10. Subjects of reproductive potential must agree to use acceptable birth control methods,
                     as described in protocol
        
                Exclusion Criteria:
        
                  1. Participation in an interventional research study within 4 weeks prior to enrollment,
                     or anticipated treatment with another investigational product while on study. This
                     refers to non-commercially approved investigational drugs different than those used in
                     this protocol.
        
                  2. Active invasive cancer other than pancreatic adenocarcinoma. Patients with active
                     non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and
                     bladder cancer, or prostate cancer with PSA level < 1.0) are not excluded.
        
                  3. HIV infection
        
                  4. Active hepatitis B or hepatitis C infection
        
                  5. Active autoimmune disease (including but not limited to: systemic lupus erythematosus,
                     Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory
                     bowel disease, etc.) requiring immunosuppressive therapy within 4 weeks prior to
                     enrollment visit, with the exception of thyroid replacement.
        
                  6. Patients with ongoing or active infection.
        
                  7. 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 or adrenal insufficiency. Corticosteroids treatment as
                     anti-emetic prophylaxis on the day of cyclophosphamide administration is allowed per
                     institutional guidance.
        
                  8. Patients requiring supplemental oxygen therapy.
        
                  9. Prior therapy with lentiviral gene modified cells.
        
                 10. History of allergy or hypersensitivity to study product excipients (human serum
                     albumin, DMSO, and Dextran 40)
        
                 11. Any clinically significant pericardial effusion, Class II-IV cardiovascular disability
                     according to the New York Heard Association Classification (see Appendix 2) or other
                     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 if cardiac issues are suspected.
        
                 12. Any clinically significant pleural or peritoneal effusion that cannot be drained with
                     standard approaches. An indwelling drainage device placed prior to enrollment is
                     acceptable.
        
                 13. Pregnant or breastfeeding women.
        
                No exceptions to eligibility will be granted.
              
        Maximum Eligible Age:N/A
        Minimum Eligible Age:18 Years
        Eligible Gender:All
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03
        Time Frame:2 years
        Safety Issue:
        Description:

        Secondary Outcome Measures

        Measure:Tumor response rates measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
        Time Frame:Day 28, Month 3, Month 6
        Safety Issue:
        Description:
        Measure:Progression-free survival (PFS)
        Time Frame:2 years
        Safety Issue:
        Description:
        Measure:Overall survival (OS)
        Time Frame:2 years
        Safety Issue:
        Description:

        Details

        Phase:Phase 1
        Primary Purpose:Interventional
        Overall Status:Recruiting
        Lead Sponsor:University of Pennsylvania

        Trial Keywords

        • metastatic adenocarcinoma, pancreas

        Last Updated

        October 26, 2017