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

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

This is a study in which pancreatic cancer patients receive a immunotherapy with CART-meso cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains.The lymphodepletion with cyclophosphamide may prolong the persistence of CART cells.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Biological: CART-meso cells

Detailed Description

This study is being conducted to assess the safety and efficacy of immunotherapy with CART-meso cells in dose escalation design. The trial will begin in Cohort 1 and progress to Cohorts 2, depending upon dose limiting toxicity (DLT) assessment .

Subjects will be enrolled serially, but infusions will be staggered to allow assessment of DLTs for determination of cohort progression, expansion, or dose de-escalation.

Cohort 1 subjects will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced CART-meso cells after conditioning chemotherapeutic regimen.

Cohort 2 subjects will receive a single dose of 1-3x10^8 /m^2 lentiviral transduced CART-meso cells cells after conditioning chemotherapeutic regimen.

Dose limiting toxicity is defined as any adverse reactions at level 3 or above that may be associated with CART-meso within 4 weeks after infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongling ZHANG, PhD; Phone Number: (+86)0755-86387905; Email: hl.zhang@bindebio.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Recruiting
      • Nanjing First Hospital
      • Contact: Jinfei CHEN, MD, PhD; Phone Number: (+86)18951670922
      • Principal Investigator: Jinfei CHEN, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (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 - 70 years of age
• 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 cells; A single dose of CART-meso T cells will be administered intravenously.The dose is 1-3×10^7/m^2 CART positive cells(chort 1)or 1-3×10^8/m^2 CART positive cells(chort 2).	Biological: CART-meso cells; CART-meso is a 2nd CAR, with mesothelin as target protein, 4-1BB as co- stimulator. The infusion will be scheduled to occur 3 (±1) days after a single dose of 1.5 grams/m^2 of cyclophosphamide, which will be administered according to standard procedures, Thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CART-meso infusion: number of adverse events	Number of Adverse Events evaluated with NCI CTC AE, version 4.0[Safety evaluation]	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response of CART-meso	Number of patients with tumor response including overal remission ,complete ression,progression-free survival，progressive disease ,etc.	60 months
CAR-T cell detection	Detection of transferred T cells in peripheral blood or bone marrow using multi-parameter flow cytometer.	60 months

Collaborators and Investigators

• Sponsor: Shenzhen BinDeBio Ltd.
• Collaborators: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Jinfei CHEN, MD, PhD, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2018
• Primary Completion (Anticipated): February 1, 2022
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: November 14, 2017
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 20, 2018

Study Record Updates

• Last Update Posted (Actual): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 2017NJYY-Meso

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No