CAR T Cells in Mesothelin Expressing Cancers
Phase I Study of Human Chimeric Antigen Receptor Modified T Cells in Patients With Mesothelin Expressing Cancers
1 other identifier
interventional
65
1 country
1
Brief Summary
Phase I study to establish safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells with or without lymphodepletion.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2017
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 9, 2017
CompletedFirst Posted
Study publicly available on registry
February 15, 2017
CompletedStudy Start
First participant enrolled
April 6, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 9, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 30, 2024
CompletedResults Posted
Study results publicly available
April 29, 2025
CompletedApril 29, 2025
April 1, 2025
6.6 years
February 9, 2017
November 8, 2024
April 25, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
7 years
Secondary Outcomes (3)
Progression-free Survival
7 years
Overall Survival
7 years
Objective Response Rate
Month 6
Study Arms (7)
Cohort 1
ACTIVE COMPARATORSingle dose of 1-3x10\^7 huCARTmeso cells/m\^2
Cohort 2
ACTIVE COMPARATORCyclophosphamide 1 gram/m\^2 administered 2-4 days prior to a single dose of 1-3x10\^7 huCARTmeso cells/m\^2
Cohort 3
ACTIVE COMPARATORPERMANENTLY CLOSED
Cohort 4
ACTIVE COMPARATORPERMANENTLY CLOSED
Cohort 5
ACTIVE COMPARATORSingle dose of 1-3x10\^7 huCART-meso cells/m\^2 day 0 by intrapleural infusion (IP) through an indwelling pleural catheter without any conditioning chemotherapeutic regimen.
Cohort 6
ACTIVE COMPARATORCyclophosphamide 1 gram/m\^2 administered 2-4 days prior to dose of 1-3x10\^7 huCART-meso cells/m\^2 via IV infusion on Day 0. This initial infusion may be followed by up to two additional IV infusions of huCART-meso cells at the same dose level, given approximately 21-42 days apart, if the subject meets eligibility to receive additional infusions. Cyclophosphamide will not be repeated prior to subsequent doses of huCART-meso cells.
Cohort 7
ACTIVE COMPARATORCyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day given over 3 days by IV infusion followed by a single dose of 1-3x10\^7 huCART-meso cells/m\^2 via intraperitoneal (i.p.) administration. Lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (+/- 1 day) prior to the infusion of huCART-meso cells. This initial i.p. infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart. The subject must meet eligibility to receive additional infusions. Lymphodepleting chemotherapy will not be repeated prior to additional infusions of huCART-meso cells.
Interventions
Intravenous administration or local delivery of lentiviral transduced huCART-meso cells in 7 cohorts with or without lymphodepletion..
Eligibility Criteria
You may qualify if:
- Histologically confirmed cancer (one of the following):
- Cohorts 1-4 and Cohort 6 participants:
- \*\*Note: Cohorts 3 and 4 permanently closed\*\*
- Metastatic or recurrent lung adenocarcinoma.
- Persistent or recurrent serous epithelial ovarian cancer or primary peritoneal carcinoma or fallopian tube carcinoma
- Malignant pleural and peritoneal mesothelioma (histologically confirmed epithelial)
- Cohort 5 participants: \*\*Note: As of 1-Feb-2021 lung adenocarcinoma patients are no longer being enrolled in this trial\*\*
- Metastatic or recurrent lung adenocarcinoma with documented pleural effusion
- Persistent or recurrent serous epithelial ovarian cancer or primary peritoneal carcinoma or fallopian tube carcinoma with documented pleural effusion
- Malignant pleural and peritoneal mesothelioma (histologically confirmed epithelial) with documented pleural effusion
- Cohort 7 patients:
- Persistent or recurrent serous epithelial ovarian cancer or primary peritoneal carcinoma or fallopian tube carcinoma with evidence of ascites
- Malignant peritoneal mesothelioma (histologically confirmed epithelial)
- CRITERIA HAS BEEN RETIRED
- Failure of at least one prior standard of care chemotherapy for advanced stage disease. ALLOWANCE FOR PRIOR PD-1 or PDL-1 THERAPIES REMOVED.
- +19 more criteria
You may not qualify if:
- Sarcomatoid and biphasic mesothelioma.
- Known leptomeningeal carcinomatosis or spinal cord compression. Screening for this is not required unless suspicious symptoms.
- Subjects with symptomatic CNS metastases are excluded.
- Active invasive cancer other than the one of the three cancers in this study. Subjects with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level \< 1.0) are not excluded.
- HIV infection
- Active hepatitis B or hepatitis C infection
- Active autoimmune disease (including but not limited to: systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within four (4) weeks prior to eligibility confirmation by physician-investigator, with the exception of thyroid replacement.
- Patients with ongoing or active infection.
- Dependence on systemic steroids or immunosupressant medications.
- Patients requiring supplemental oxygen therapy.
- Prior therapy with lentiviral gene modified cells.
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis, or which may worsen as a result of expected toxicities in this study. This determination will be made by a cardiologist if cardiac issues are suspected.
- Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to eligibility confirmation by physician / investigator is acceptable.
- Pregnant or breastfeeding women.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Regulatory Lead
- Organization
- University of Pennsylvania
Study Officials
- PRINCIPAL INVESTIGATOR
Janos L Tanyi, MD, PhD
University of Pennaylvania
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 9, 2017
First Posted
February 15, 2017
Study Start
April 6, 2017
Primary Completion
November 9, 2023
Study Completion
July 30, 2024
Last Updated
April 29, 2025
Results First Posted
April 29, 2025
Record last verified: 2025-04