Clinical trial NCT03638193: Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer
Official title: Study of Autologous T-cells Redirected to Mesothelin With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pancreatic Cancer
Lead sponsor: Shenzhen BinDeBio Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital with Nanjing Medical University
First posted: 2018-08-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

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 - 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

Primary outcomes:
measure: Safety of CART-meso infusion: number of adverse events
timeFrame: 60 months
Secondary outcomes:
measure: Clinical response of CART-meso
timeFrame: 60 months
measure: CAR-T cell detection
timeFrame: 60 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Jinfei CHEN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: