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Pilot Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer

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: NCT02465983
Recruitment Status : Terminated (Lack of efficacy and funding to continue investigation)
First Posted : June 9, 2015
Last Update Posted : December 16, 2019
Sponsor:
Collaborator:
University of California, San Francisco
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE May 28, 2015
First Posted Date  ICMJE June 9, 2015
Last Update Posted Date December 16, 2019
Study Start Date  ICMJE May 2015
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2015)
Safety of IV administration of CART-meso-19 with cyclophosphamide as lymphodepleting chemotherapy in patients with pancreatic cancer using the NCI CTCAE v4.03 criteria [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
  • Safety of IV administration of CART-meso-19 with cyclophosphamide as lymphodepleting chemotherapy in patients with pancreatic cancer using the NCI CTCAE v4.03 criteria [ Time Frame: 24 months ]
  • Feasibility of IV administration of CART-meso-19 with cyclophosphamide as lymphodepleting chemotherapy in patients with pancreatic cancer [ Time Frame: 24 months ]
    Composite measure of clinical and manufacturing feasibility of IV administration of CART-meso-19 with cyclophosphamide measured by frequency of subjects who do not receive CART-meso-19 cells and the rate of manufacturing failures
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
  • Clinical Response as determined by radiographic imaging (RECIST1.1) and serum biomarkers [ Time Frame: Up to 2 years ]
  • Correlative Analysis [ Time Frame: Up to 2 years ]
    Composite measurement of the following:
    1. persistence of CART-meso and CART19 cells in peripheral blood by qPCR at day 28
    2. bioactivity of CART-meso and CART19 cells by cytokine analysis of peripheral blood and fluids
    3. B cell aplasia
    4. immune responses favoring rejection of CART-meso cells by humoral and cellular analysis
    5. secondary anti-tumor responses as a consequence of epitope spreading
    6. tumor biomarker levels (CA19-9, CEA, SMRP, fibulin) as surrogate of CART-meso activity
    7. presence of immune cells, CART cells and mesothelin expression in tumor tissues and fluids as available
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer
Official Title  ICMJE Pilot Study of Autologous T-cells Redirected to Mesothelin and CD19 With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer
Brief Summary This is a study in which pancreatic cancer patients receive a combination therapy with CART-meso cells and CART19 cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells that were modified in the laboratory to express a receptor specific to the mesothelin protein. CART19 cells are patients' own T cells that were modified in the laboratory to express a receptor specific to a protein called CD19. The CD19 protein is expressed on white blood B cells. CART19 cells are expected to attack the B cells and impede the antibody response against CART-meso cells. The investigators hypothesize that this combination therapy may prolong the duration of CART-meso cells in the body. Additionally, one dose of cyclophosphamide may enhance engraftment and persistence of CART cells.
Detailed Description

Immunotherapy is a novel and promising approach for the treatment of solid tumors; immunotherapy with chimeric antigen receptor (CAR) T cells (CART cells) in particular has the potential advantage of targeted therapies that can invoke a rapid tumor response, and the advantage of long-lived responses that are the hallmark of engagement of the adaptive immune system such as memory T cells.

This is a single arm, open-label, phase I study to determine the safety and feasibility of combination CART-meso cells (autologous T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains) and CART19 cells (autologous T cells lentivirally transduced to express a humanized anti-CD19 scFv fused to TCRζ and 4-1BB costimulatory domains) in patients with pancreatic cancer following lymphodepletion with cyclophosphamide.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • Biological: CART-meso-19 T cells
    A single dose of CART-meso-19 cells (combination therapy with CART-meso and CART19 cells) will be administered intravenously as two separate infusions. The dose is 1-3x107/m2 (Cohort 1) or 1-3x108/m2 (Cohort 2) CART positive cells. The infusion will be scheduled to occur 3 (±1) days after a single dose of 1.5 grams/m2 of cyclophosphamide, which will be administered according to standard procedures in the outpatient setting. Patients will receive CART cell treatment on an outpatient basis.
  • Drug: Cyclophosphamide
    A single dose of chemotherapy to be administered prior to dosing of the CART-meso-19 cells
Study Arms  ICMJE Experimental: CART-meso-19 T cells
A single dose of CART-meso-19 T cells (combination therapy with CART-meso and CART19 cells) will be administered intravenously as two separate infusions. The dose is 1-3x107/m2 (Cohort 1) or 1-3x108/m2 (Cohort 2) CART positive cells. The infusion will be scheduled to occur 3 (±1) days after a single dose of 1.5 grams/m2 of cyclophosphamide, which will be administered according to standard procedures in the outpatient setting.
Interventions:
  • Biological: CART-meso-19 T cells
  • Drug: Cyclophosphamide
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 Terminated
Actual Enrollment  ICMJE
 (submitted: December 11, 2017)
4
Original Estimated Enrollment  ICMJE
 (submitted: June 4, 2015)
12
Actual Study Completion Date  ICMJE November 2017
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent
  • Unresectable or metastatic pancreatic cancer
  • Persistent cancer after at least one prior standard of care chemotherapy for advanced stage disease
  • 18 years of age and older
  • ECOG performance status of 0 or 1
  • Life expectancy greater than 3 months
  • Satisfactory organ and bone marrow function
  • Meets blood coagulation parameters
  • Male and Female subjects of reproductive potential agree to use approved contraceptive methods

Exclusion Criteria:

  • Participation in a therapeutic investigational study within 4 weeks prior to the screening visit
  • Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion
  • Active invasive cancer other than pancreatic cancer
  • HIV, HCV, or HBV infections
  • Active autoimmune disease requiring immunosuppressive therapy within 4 weeks prior to screening visit, with exception of thyroid replacement
  • Ongoing or active infection
  • Planned concurrent treatment with systemic high dose corticosteroids
  • Patients requiring supplemental oxygen therapy
  • Prior therapy with gene modified cells
  • Previous experimental therapy with SS1 moiety, murine or chimeric antibodies
  • History of allergy to murine proteins
  • History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
  • Clinically significant pericardial effusion, CHF, or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study
  • Pregnant or breastfeeding women
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 NCT02465983
Other Study ID Numbers  ICMJE UPCC 19214, 821275
UPCC 19214 ( Other Identifier: University of Pennsylvania Cancer Center )
UCSF CC144520 ( Other Identifier: University of California San Francisco Cancer Center )
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 University of California, San Francisco
Investigators  ICMJE
Study Director: Gabriela Plesa University of Pennsylvania
Principal Investigator: Andrew Ko University of California, San Francisco
PRS Account University of Pennsylvania
Verification Date December 2019

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