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

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ClinicalTrials.gov Identifier: NCT02465983
Recruitment Status : Completed
First Posted : June 9, 2015
Last Update Posted : June 29, 2018
Sponsor:
Collaborator:
University of California, San Francisco
Information provided by (Responsible Party):
University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Biological: CART-meso-19 T cells Drug: Cyclophosphamide Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Autologous T-cells Redirected to Mesothelin and CD19 With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer
Study Start Date : May 2015
Actual Primary Completion Date : September 2017
Actual Study Completion Date : November 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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 ]


Information from the National Library of Medicine

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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:

  • 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

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): NCT02465983


Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94158
Sponsors and Collaborators
University of Pennsylvania
University of California, San Francisco
Investigators
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Study Director: Gabriela Plesa University of Pennsylvania
Principal Investigator: Andrew Ko University of California, San Francisco

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02465983     History of Changes
Other Study ID Numbers: UPCC 19214, 821275
UPCC 19214 ( Other Identifier: University of Pennsylvania Cancer Center )
UCSF CC144520 ( Other Identifier: University of California San Francisco Cancer Center )
First Posted: June 9, 2015    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018

Keywords provided by University of Pennsylvania:
Pancreatic Cancer
CAR / CART
T cells
Immunotherapy
Gene therapy
Redirected T cells
Autologous T cells

Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists