search
Back to results

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

Primary Purpose

Pancreatic Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CART-meso-19 T cells
Cyclophosphamide
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring Pancreatic Cancer, CAR / CART, T cells, Immunotherapy, Gene therapy, Redirected T cells, Autologous T cells

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, San Francisco

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CART-meso-19 T cells

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
May 28, 2015
Last Updated
December 12, 2019
Sponsor
University of Pennsylvania
Collaborators
University of California, San Francisco
search

1. Study Identification

Unique Protocol Identification Number
NCT02465983
Brief Title
Pilot Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy and funding to continue investigation
Study Start Date
May 2015 (undefined)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
University of California, San Francisco

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
Pancreatic Cancer, CAR / CART, T cells, Immunotherapy, Gene therapy, Redirected T cells, Autologous T cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CART-meso-19 T cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CART-meso-19 T cells
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
A single dose of chemotherapy to be administered prior to dosing of the CART-meso-19 cells
Primary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriela Plesa
Organizational Affiliation
University of Pennsylvania
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Andrew Ko
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs