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CAR T Cell Immunotherapy for Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT03323944
Recruitment Status : Active, not recruiting
First Posted : October 27, 2017
Last Update Posted : February 19, 2018
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Cancer of the Pancreas Biological: huCART-meso cells Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Human Chimeric Antigen Receptor Modified T Cells (CAR T Cells) in Patients With Pancreatic Cancer
Actual Study Start Date : September 15, 2017
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: huCART-meso cells only
Subjects will receive a single dose of 1-3x10^7/m^2 lentiviral transduced huCART-meso cells without any conditioning chemotherapeutic regimen.
Biological: huCART-meso cells
Intravenous administration of permanently modified CAR T cells that target mesothelin, given as single agent or in combination with a lymphodepleting dose of cyclophosphamide.

Experimental: Cohort 2: huCART-meso cells only
Subjects will receive a single dose of 1-3x10^8/m^2 lentiviral transduced huCART-meso cells without any conditioning chemotherapeutic regimen.
Biological: huCART-meso cells
Intravenous administration of permanently modified CAR T cells that target mesothelin, given as single agent or in combination with a lymphodepleting dose of cyclophosphamide.

Experimental: Cohort 3: huCART-meso cells after chemo
Subjects 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.
Biological: huCART-meso cells
Intravenous administration of permanently modified CAR T cells that target mesothelin, given as single agent or in combination with a lymphodepleting dose of cyclophosphamide.




Primary Outcome Measures :
  1. Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Tumor response rates measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria [ Time Frame: Day 28, Month 3, Month 6 ]
  2. Progression-free survival (PFS) [ Time Frame: 2 years ]
  3. Overall survival (OS) [ Time Frame: 2 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


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): NCT03323944


Locations
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Mark O'Hara, MD Assistant Professor of Medicine, Penn Medicine

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03323944     History of Changes
Other Study ID Numbers: 827664
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: February 19, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Pennsylvania:
metastatic adenocarcinoma, pancreas

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases