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: 827644 (UPCC 14217)
  • NCT ID: NCT03323944

Conditions

  • Pancreatic Cancer
  • Cancer of the Pancreas

Interventions

DrugSynonymsArms
huCART-meso cellsCohort 1: huCART-meso cells without lymphodepletion

Purpose

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.

Detailed Description

      This is a Phase I study evaluating the feasibility of producing as well as the safety of
      administering lentiviral transduced huCART-meso cells in up to three (3) cohorts both with
      and without cyclophosphamide in a three-plus-three (3+3) dose escalation design.

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

           - If one (1) Dose Limiting Toxicity (DLT) occur in three (3) subjects, the study will
           enroll an additional three (3) subjects at the same dose level. If zero (0) DLTs occur
           in three (3) subjects, or if one (1) DLT occurs in six (6) subjects, the study will
           begin to enroll subjects into Cohort 2. However, if two (2) DLTs occur at this dose
           level at any time, enrollment in Cohort 1 will be stopped, and the administered dose
           will be de-escalated by 10-fold to 1-3x10^6 cells/m^2, and enrollment into Cohort -1
           will begin.

        -  Cohort 2 (N=3-6): subjects will receive a single dose of 1-3x10^7/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 huCART-meso cells (~day -4 to day -2).

           - If zero (0) or one (1) DLTs occur in three (3) subjects, the study will enroll an
           additional three (3) subjects to confirm tolerability. If two (2) DLTs occur in three
           (3) subjects or two (2) DLTs occur in six (6) subjects, further infusions in this cohort
           will be halted.

        -  Cohort -1 (N=3-6): subjects will receive a single dose of 1-3x10^6 cells/m^2 lentiviral
           transduced huCART-meso cells on day 0 without any conditioning chemotherapeutic regimen.
           Up to six (6) subjects will be infused in Cohort -1 with not more than one (1) DLT
           occurring in six (6) subjects to establish the Maximum Tolerated Dose (MTD).

      These cohorts will be used to establish the safety of this investigational product
      (huCART-meso cells) as well as the target dose level in the target study population. If
      safety is established, the study will be further amended to explore the safety of local
      delivery methods.

      Adverse events will be collected and evaluated during the protocol specified adverse event
      reporting period.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: huCART-meso cells without lymphodepletionExperimentalSubjects will receive a single dose of 1-3x10^7/m^2 lentiviral transduced huCART-meso cells without any conditioning chemotherapeutic regimen.
  • huCART-meso cells
Cohort 2: huCART-meso cells following lymphodepletionExperimentalSubjects will receive a single dose of 1-3x10^7/m^2 lentiviral transduced huCART-meso cells following a flat dose of 1 gram/m^2 of cyclophosphamide administered 2-4 days prior to huCART-meso cells (approximately day -4 to day -2).
  • huCART-meso cells
Cohort -1: low-dose huCART-meso cells without lymphodepletionExperimentalSubjects will receive a single dose of 1-3x10^6 cells/m^2 lentiviral transduced huCART-meso cells on day 0 without any conditioning chemotherapeutic regimen.
  • huCART-meso cells

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 measurable disease as defined by RECIST 1.1 criteria.

               5. Subjects must be greater than eighteen (> 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:

                    -  Absolute neutrophil count must not be less than one thousand cells per
                       microliter (≥1,000/μL)

                    -  Platelets must be greater than seventy five thousand per micro liter
                       (>75,000/μL)

                    -  Hemoglobin must be greater than nine grams per deciliter (> 9 g/dL)

                    -  Bilirubin must be less than two times (< 2.0x) the institutional normal
                       upper limit

                    -  Creatinine must be less than one and one half times (< 1.5x) the
                       institutional normal upper limit

                    -  Albumin must not be less than two (≥ 2)

                    -  Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
                       must be less than five times (< 5x) the institutional normal upper limit

                    -  Cardiac ejection fraction of greater than forty percent (>40%) as measured
                       by resting echocardiogram, with no clinically significant pericardial
                       effusion.

               8. Blood coagulation parameters: PT such that international normalized ratio (INR)
                  is not greater than one and one half (≤ 1.5) and a PTT must be less than one and
                  two-tenths times (< 1.2x) the upper limit of normal unless the subject is
                  therapeutically anti-coagulated for history of cancer-related thrombosis and has
                  stable coagulation parameters.

               9. Subjects must provide written informed consent.

              10. Subjects of reproductive potential must agree to use acceptable birth control
                  methods

          -  Exclusion Criteria:

               1. Participation in an interventional research study within four (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. Subjects with active
                  non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and
                  bladder cancer, or prostate cancer with PSA level less than one (< 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 four (4) weeks prior to enrollment visit, with the exception of thyroid
                  replacement.

               6. Subjects with ongoing or active infection.

               7. Planned concurrent treatment with systemic high dose corticosteroids. Subjects
                  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 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

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