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Autologous Redirected RNA Meso CAR T Cells for Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT01897415
Recruitment Status : Completed
First Posted : July 12, 2013
Last Update Posted : September 19, 2017
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE July 9, 2013
First Posted Date  ICMJE July 12, 2013
Last Update Posted Date September 19, 2017
Study Start Date  ICMJE July 2013
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
Number of Adverse Events [ Time Frame: Day 28 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01897415 on ClinicalTrials.gov Archive Site
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 Autologous Redirected RNA Meso CAR T Cells for Pancreatic Cancer
Official Title  ICMJE Phase I Clinical Trial of Autologous Mesothelin Re-directed T Cells in Patients With Chemotherapy Refractory Metastatic Pancreatic Cancer
Brief Summary This is a Phase I safety and feasibility study. Subjects will be enrolled serially. For subject safety, the preceding subject must have completed one cycle of therapy (28 days) before the next subject can be treated. Subjects will be treated with i.v. administration of 1 to 3e8 per meter squared RNA CAR T cells three times weekly (M-W-F) for three weeks.
Detailed Description

This phase I study is being conducted to establish safety and feasibility of intravenous (IV) RNA mesothelin re-directed autologous T cell administration in patients with chemotherapy-refractory metastatic pancreatic cancer.

Subjects will be enrolled serially. For subject safety, the preceding subject must have completed therapy and be 28 days from their last infusion before the next subject can be treated.. Subjects will be treated with IV administration of 1 to 3e8/m2 RNA CAR T cells three times weekly (M-W-F) for three weeks.

Main eligibility criteria: Subjects with metastatic pancreatic ductal adenocarcinoma (PDA) who have chemotherapy-refractory disease. Inclusion criteria include patients older than 18 years of age diagnosed with metastatic PDA with ECOG 0-1 performance status and 3 month expected survival. Exclusion criteria include a pericardial effusion, active autoimmune disease requiring immunosuppressive therapy, active anti-coagulation therapy, known HIV or HTLV I/II positivity, prior treatment with murine monoclonal antibodies or history of allergy to murine proteins.

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 Subjects With Metastatic Pancreatic Ductal Adenocarcinoma (PDA)
Intervention  ICMJE Biological: Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1
Study Arms  ICMJE Experimental: Autologous T cells
Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1
Intervention: Biological: Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1
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 16, 2016)
16
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2013)
10
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed metastatic pancreatic adenocarcinoma.
  • Patients greater than or equal to 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy greater than 3 months.
  • Evidence of metastatic disease and failure of at least 1 prior chemotherapy for metastatic disease.
  • Subjects must have measureable disease as defined by RECIST 1.1 criteria.
  • Satisfactory organ and bone marrow function
  • Blood coagulation parameters: PT such that international normalized ratio (INR) is less than or equal to 1.5 (or an in-range INR, usually between 2 and 3, if a subject is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT less than or equal to 1.2 time the upper limit of normal.
  • Subjects must have adequate venous peripheral access for apheresis. Patients must also have adequate venous access for subsequent modified CAR T cell administration which can be done through a central venous access (e.g. port for systemic chemotherapy)
  • Ability to understand and the willingness to provide written informed consent.
  • Short-term therapy for acute conditions not specifically related to pancreatic cancer is allowed if such therapy does not include immune modulating agents.
  • Male and Female subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for 3 months following the last dose of the study cell infusion.
  • Subject must understand and sign the study-specific informed consent.

Exclusion Criteria:

  • Participated in any other trial in which receipt of an investigational study drug occurred within 28 days (42 days for non-murine monoclonal antibodies) prior to entry into the study.
  • Received any anticancer medication in the 2 weeks (i.e. 14 days) prior to receiving their first dose of study treatment and no other concurrent chemotherapy or immunotherapy (e.g. monoclonal antibodies)
  • Active invasive cancer other than pancreatic adenocarcinoma. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level less than 1.0) are not excluded.
  • Known HIV, HCV, and HBV positive
  • Active autoimmune disease (including but not limited to: systemic lupus erythromatosis, Sjogrens 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.
  • Prior gene therapy or therapy with murine monoclonal antibodies or products of murine origin.
  • Concurrent treatment with any anticancer agent.
  • 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.
  • Subjects on active anti-coagulation therapy.
  • Pregnant women are excluded from this study because autologous transduced T cells may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with autologous transduced T cells, breastfeeding should be discontinued if the mother is treated.
  • Feasibility assessment demonstrates less than 20% transfection of target lymphocytes or insufficient expansion of modified CAR T cells to complete 9 infusions.
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 NCT01897415
Other Study ID Numbers  ICMJE UPCC 08212
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: Gregory Beatty, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date September 2017

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