Pilot Study Of Autologous T-cells In Patients With Metastatic Pancreatic Cancer

Study Overview

Pilot Study of Autologous T-cells 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.

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.

Pancreatic Cancer

BIOLOGICAL: CART-meso-19 T cells
DRUG: Cyclophosphamide

UPCC 19214, 821275
UPCC 19214 (OTHER Identifier) (OTHER: University of Pennsylvania Cancer Center)
UCSF CC144520 (OTHER Identifier) (OTHER: University of California San Francisco Cancer Center)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-05-28	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-12-12
First Submitted that Met QC Criteria 2015-06-04	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-12-16
First Posted (ACTUAL) 2015-06-09	Results First Posted N/A	Last Verified 2019-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

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	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 sc DRUG: Cyclophosphamide A single dose of chemotherapy to be administered prior to dosing of the CART-meso-19 cells

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

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 sc

DRUG: Cyclophosphamide

A single dose of chemotherapy to be administered prior to dosing of the CART-meso-19 cells

Primary Outcome Measures	Measure Description	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

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

University of California, San Francisco

Investigators

STUDY_DIRECTOR: Gabriela Plesa, University of Pennsylvania

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

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Caregivers

Clinical Trial Record