Clinical trial NCT03497819: Autologous CARTmeso/19 Against Pancreatic Cancer
Official title: Pilot Study of Autologous Chimeric Antigen Receptor Cells Against Mesothelin and CD19 in Patients With Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Pancreatic Cancer
Keywords: CART
Pancreatic Cancer
artery infusion
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2018-04-13
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Pancreatic cancer patients receive chimeric antigen receptor (CAR) T cells against mesothelin (CARTmeso) or CD19 (CART19) cells administered at 3 days via pancreatic artery infusion or i.v. after preconditioning of cyclophosphamide. Both CART cells are autologous. CARTmeso cells target pancreatic cells which highly express mesothelin, while CART19 cells target tumor-associated B cells expressing cluster of differentiation antigen 19 (CD19) which are mostly immunosuppressive. The investigators hypothesize that this combination therapy may enhance the efficacy of CARTmeso cells in the body. Additionally, a medium dose of cyclophosphamide is used to enhance the engraftment of CART cells.

Detailed description: This is a single arm, open-label, pilot study to determine the safety and feasibility of combination CARTmeso cells and CART19 cells in patients with pancreatic cancer following lymphodepletion with cyclophosphamide. Both cells contain CAR proteins consisting of a murine-derived single chain antibody fragment (scFv), cluster of differentiation antigen 137 (41BB) co-stimulatory domain and cluster of differentiation antigen 3 zeta chain (CD3ζ) signaling domain transduced by lentivirus

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* serum soluble mesothelin-related protein (SMRP) \> 0.4 nanomolar/L
* Persistent cancer after at least one prior standard of care chemotherapy for advanced stage disease

  * 18 years of age and ≤65
* Life expectancy greater than 3 months
* Satisfactory organ and bone marrow function

Exclusion Criteria:

* Participation in a therapeutic investigational study within 4 weeks prior to the screening visit
* Active invasive cancer other than pancreatic cancer
* HIV, hepatitis B/C virus, or infections
* Active autoimmune disease requiring immunosuppressive therapy within 4 weeks
* Planned concurrent treatment with systemic high dose corticosteroids
* Patients requiring supplemental oxygen therapy
* Pregnant or breastfeeding women

Primary outcomes:
measure: The Percentage of Adverse Events (AEs) ≥ grade 3 assessed through MedDra and CTCAE v4.03 [Time frame: from infusion to 3 month afterward]
timeFrame: From first infusion to 3 months afterward
Secondary outcomes:
measure: Overall Response Rate defined as any improvement measured by imaging following RECIST 1.1 [Time Frame: Day 14 and 1 month after infusion]
timeFrame: Day 14 and 1 month after infusion, or until patient withdraw consent or receive new therapy
Other outcomes:
Locations:
city: Wenzhou
country: China
facility: First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Wenzhou Medical University
name: Mengtao Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: