- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01897415
Autologous Redirected RNA Meso CAR T Cells for Pancreatic Cancer
Phase I Clinical Trial of Autologous Mesothelin Re-directed T Cells in Patients With Chemotherapy Refractory Metastatic Pancreatic Cancer
Study Overview
Status
Intervention / Treatment
Detailed Description
This phase I study is being conducted to establish safety and feasibility of intravenous (IV) RNA mesothelin re-directed autologous T cell administration in patients with chemotherapy-refractory metastatic pancreatic cancer.
Subjects will be enrolled serially. For subject safety, the preceding subject must have completed therapy and be 28 days from their last infusion before the next subject can be treated.. Subjects will be treated with IV administration of 1 to 3e8/m2 RNA CAR T cells three times weekly (M-W-F) for three weeks.
Main eligibility criteria: Subjects with metastatic pancreatic ductal adenocarcinoma (PDA) who have chemotherapy-refractory disease. Inclusion criteria include patients older than 18 years of age diagnosed with metastatic PDA with ECOG 0-1 performance status and 3 month expected survival. Exclusion criteria include a pericardial effusion, active autoimmune disease requiring immunosuppressive therapy, active anti-coagulation therapy, known HIV or HTLV I/II positivity, prior treatment with murine monoclonal antibodies or history of allergy to murine proteins.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Abramson Cancer Center of the University of Pennsylvania
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed metastatic pancreatic adenocarcinoma.
- Patients greater than or equal to 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy greater than 3 months.
- Evidence of metastatic disease and failure of at least 1 prior chemotherapy for metastatic disease.
- Subjects must have measureable disease as defined by RECIST 1.1 criteria.
- Satisfactory organ and bone marrow function
- Blood coagulation parameters: PT such that international normalized ratio (INR) is less than or equal to 1.5 (or an in-range INR, usually between 2 and 3, if a subject is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT less than or equal to 1.2 time the upper limit of normal.
- Subjects must have adequate venous peripheral access for apheresis. Patients must also have adequate venous access for subsequent modified CAR T cell administration which can be done through a central venous access (e.g. port for systemic chemotherapy)
- Ability to understand and the willingness to provide written informed consent.
- Short-term therapy for acute conditions not specifically related to pancreatic cancer is allowed if such therapy does not include immune modulating agents.
- Male and Female subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for 3 months following the last dose of the study cell infusion.
- Subject must understand and sign the study-specific informed consent.
Exclusion Criteria:
- Participated in any other trial in which receipt of an investigational study drug occurred within 28 days (42 days for non-murine monoclonal antibodies) prior to entry into the study.
- Received any anticancer medication in the 2 weeks (i.e. 14 days) prior to receiving their first dose of study treatment and no other concurrent chemotherapy or immunotherapy (e.g. monoclonal antibodies)
- Active invasive cancer other than pancreatic adenocarcinoma. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level less than 1.0) are not excluded.
- Known HIV, HCV, and HBV positive
- Active autoimmune disease (including but not limited to: systemic lupus erythromatosis, Sjogrens syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within the past 4 weeks, with exception of thyroid replacement.
- Patients with ongoing or active infection.
- Planned concurrent treatment with systemic high dose corticosteroids.
- Prior gene therapy or therapy with murine monoclonal antibodies or products of murine origin.
- Concurrent treatment with any anticancer agent.
- History of allergy to murine proteins
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- Any clinically significant pericardial effusion; CHF (NY Heart Association Grade II-IV) or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis.
- Subjects on active anti-coagulation therapy.
- Pregnant women are excluded from this study because autologous transduced T cells may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with autologous transduced T cells, breastfeeding should be discontinued if the mother is treated.
- Feasibility assessment demonstrates less than 20% transfection of target lymphocytes or insufficient expansion of modified CAR T cells to complete 9 infusions.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Autologous T cells
Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of Adverse Events
Time Frame: Day 28
|
Day 28
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Gregory Beatty, MD, Abramson Cancer Center of the University of Pennsylvania
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- UPCC 08212
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Subjects With Metastatic Pancreatic Ductal Adenocarcinoma (PDA)
-
Georgetown UniversityERYtech PharmaActive, not recruitingMetastatic Pancreatic Ductal Adenocarcinoma | Locally Advanced Pancreatic Ductal AdenocarcinomaUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingPancreatic Cancer | Pancreatic Cancer Metastatic | Pancreatic Cancer Stage IV | Metastatic Pancreatic Carcinoma | Metastatic Pancreatic Adenocarcinoma | Pancreatic Carcinoma | Metastatic Pancreatic Cancer | Pancreatic Cancer Non-resectable | Metastatic Pancreatic Ductal Adenocarcinoma | Pancreatic Carcinoma... and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingPancreatic Cancer | Pancreatic Ductal Adenocarcinoma | Metastatic Pancreatic Cancer | Metastatic Pancreatic Ductal Adenocarcinoma | Primary Pancreatic Ductal AdenocarcinomaUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingPancreatic Cancer | Pancreatic Cancer Metastatic | Pancreatic Ductal Adenocarcinoma | Pancreatic Carcinoma | Metastatic Pancreatic Cancer | Metastatic Pancreatic Ductal AdenocarcinomaUnited States
-
Roswell Park Cancer InstituteNot yet recruitingStage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Metastatic Pancreatic Ductal Adenocarcinoma | Locally Advanced Pancreatic Ductal Adenocarcinoma | Advanced Pancreatic Ductal Adenocarcinoma | Unresectable Pancreatic Ductal Adenocarcinoma and other conditionsUnited States
-
Sierra Oncology LLC - a GSK companyTerminatedMetastatic Pancreatic Ductal AdenocarcinomaUnited States
-
PfizerCelgeneCompletedMetastatic Pancreatic Ductal AdenocarcinomaUnited States, Spain
-
Georgetown UniversityMerck Sharp & Dohme LLC; BioXcel Therapeutics IncRecruitingMetastatic Pancreatic Ductal AdenocarcinomaUnited States
-
National University Hospital, SingaporeRecruitingMetastatic Pancreatic Ductal AdenocarcinomaSingapore
-
Novartis PharmaceuticalsActive, not recruitingMetastatic Pancreatic Ductal AdenocarcinomaUnited States, China, Hungary, Taiwan, Belgium, Germany, Spain, Italy, Czechia, France, Japan, Switzerland, Australia, Israel, Korea, Republic of, Canada, Russian Federation, Slovakia, United Kingdom, Turkey, Sweden, Greece, Finland, ... and more
Clinical Trials on Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1
-
Verismo TherapeuticsRecruitingOvarian Cancer | Mesothelioma, Malignant | Cholangiocarcinoma RecurrentUnited States
-
Massachusetts General HospitalNational Institute of Allergy and Infectious Diseases (NIAID)CompletedHIV Infections | HIV-1 InfectionUnited States
-
PersonGen BioTherapeutics (Suzhou) Co., Ltd.Anhui Provincial Hospital; The First People's Hospital of Hefei; Hefei Binhu...UnknownFollicular Lymphoma | Mantle Cell Lymphoma | Chronic Lymphocytic Leukemia | Acute Lymphocytic Leukemia | Diffuse Large Cell Lymphoma | B-cell Prolymphocytic LeukemiaChina
-
PersonGen BioTherapeutics (Suzhou) Co., Ltd.Anhui Provincial HospitalUnknownFollicular Lymphoma | Mantle Cell Lymphoma | Chronic Lymphocytic Leukemia | Acute Lymphocytic Leukemia | Diffuse Large Cell Lymphoma | B-cell Prolymphocytic LeukemiaChina
-
Chinese PLA General HospitalUnknownRelapsed Adult Myeloid Leukemia | Chemotherapy Refractory Adult Myeloid LeukemiaChina
-
The First Affiliated Hospital of Soochow UniversityShanghai Unicar-Therapy Bio-medicine Technology Co.,LtdRecruiting
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | Recurrent Mantle Cell Lymphoma | Metastatic Lung Non-Small Cell Carcinoma | Refractory Chronic Lymphocytic Leukemia | Stage IIIA Lung Non-Small Cell Cancer AJCC v7 | Recurrent Acute Lymphoblastic Leukemia | Metastatic Triple-Negative... and other conditionsUnited States
-
Beijing Boren HospitalRecruitingAcute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia, in Relapse | Refractory Acute Lymphoblastic LeukemiaChina
-
Beijing Boren HospitalRecruitingAcute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Refractory Acute Lymphoblastic LeukemiaChina
-
Sara V. LatorreInstituto de Salud Carlos III; Fondos ARI (Assistencia Recerca Intensiva); Fondo...Active, not recruiting