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

Pilot Study of Autologous T-cells Redirected to Mesothelin and CD19 With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Biological: CART-meso-19 T cells; Drug: Cyclophosphamide

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: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	24 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: University of California, San Francisco
• Investigators: Study Director: Gabriela Plesa, University of Pennsylvania; Principal Investigator: Andrew Ko, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 9, 2015

Study Record Updates

• Last Update Posted (Actual): December 16, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Immunotherapy; Pancreatic Cancer; Gene therapy; T cells; CAR / CART; Redirected T cells; Autologous T cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• 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)