Phase I Study of Human Chimeric Antigen Receptor Modified T Cells (CAR T Cells) in Patients With Pancreatic Cancer

University of Pennsylvania2 个研究点分布在 1 个国家目标入组 54 人开始时间: 2017年9月15日最近更新: 2026年1月30日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: University of Pennsylvania
入组人数: 54
试验地点: 2
主要终点: Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

Phase I study to establish the safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells in patients with histologically confirmed unresectable or metastatic pancreatic adenocarcinoma

详细描述

This is a Phase I study evaluating the safety and feasibility of lentiviral transduced huCART-meso cells in up to 4 cohorts. Lymphodepleting chemotherapy will not be utilized as part of the planned dosing strategy.

• Cohort 1 (N=3-6): will receive a single dose of 1-3x10^7/m^2 lentiviral transduced huCART-meso cells on day 0 via intravenous infusion.

Enrollment into Cohort 1 will be paused after the 3rd subject is infused to allow for a formal DLT assessment (performed by the Clinical PI and Medical Director) and DSMB review. If 1 DLT/3 subjects occurs in Cohort 1, the Sponsor (with guidance from the DSMB), will determine whether the study will enroll an additional 3 subjects at this dose level to further establish safety via intravenous infusion, or advance to Cohorts 2 and 3 to explore local delivery of huCART-meso cells at the same dose level. If 0 DLT/3 subjects or 1 DLT/6 subjects occurs at any time, the study may advance to Cohorts 2 and 3.
If 2 DLTs occur at this dose level at any time, enrollment in Cohort 1 will be stopped and the dose will be de-escalated by 10-fold to 1-3x10^6 cells/m^2 (Cohort -1).
The infusions in Cohort 1 will be staggered by at least 28 days to allow for the assessment of DLTs for cohort progression, expansion, or dose de-escalation.

In the event that 2 DLTs occur among subjects enrolled in Cohort 1, then enrollment in Cohort 1 will be stopped and the dose will be de-escalated by 10-fold to 1-3x10^6 cells/m^2. This de-escalated cohort will be designated Cohort -1.

• Cohort -1 (N=3-6): will receive a single dose of 1-3x10^6 cells/m^2 lentiviral transduced huCART-meso cells on day 0. Up to 6 subjects will be infused in Cohort -1 if ≤ 1 DLT occurs.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Inclusion Criteria
•Patients with the following diagnoses:
•Cohorts 1 and -1: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma
•Cohort 2: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; and either cytologically-proven ascites or known peritoneal disease on radiologic imaging.
•Cohort 3 - 4: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma with liver metastases as confirmed by pathology or radiographic imaging.
•INCLUSION CRITERIA HAS BEEN RETIRED
•Prior treatment requirements:
•Cohorts 1 - 3: Failure of at least one prior standard of care chemotherapy for advanced stage disease.
•Cohort 4: At lease stable disease on the first-line standard of care chemotherapy for advanced stage disease.
•Cohorts 1-3 and -1: Subjects must have measurable disease as defined by RECIST 1.1 criteria.
•Patients ≥ 18 years of age.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
•Satisfactory organ and bone marrow function as defined by the following:
•i. Absolute neutrophil count ≥ 1,000/μl ii. Platelets ≥75,000/μl iii. Hemoglobin ≥ 8 g/dL iv. Direct bilirubin ≤ 2.0 mg/dl unless the subject has Gilbert's disease syndrome (≤ 3.0 mg.dl) v. Creatinine ≤ 1.5x the institutional normal upper limit vi. Albumin ≥ 2 vii. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5x the institutional normal upper limit viii. Cardiac ejection fraction of ≥40% as measured by resting echocardiogram, with no clinically significant pericardial effusion.
•Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT ≤ 1.2 time the upper limit of normal unless the patient is therapeutically anti-coagulated for history of cancer-related thrombosis and has stable coagulation parameters.
•Provides written informed consent.
•Subjects of reproductive potential must agree to use acceptable birth control methods

排除标准

•EXCLUSION CRITERIA HAS BEEN RETIRED
•Active invasive cancer other than pancreatic adenocarcinoma. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder cancer, or 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 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 immunosuppressant 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 that may worsen as a result of toxicities expected for 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.
•EXCLUSION CRITERIA HAS BEEN RETIRED
•EXCLUSION CRITERIA HAS BEEN RETIRED
•Patients with significant lung disease as follows:
•Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden. Note: "Greater than lobar" = "in more than 1 lobe".
•Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
•Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc)
•Patients with radiographic evidence of significant pleural effusion that is not readily amenable to minimally invasive drainage.
•17. Cohort 3 and 4 Subjects Only: Patients with a contraindication to IV contrast.

研究组 & 干预措施

Cohort 1: huCART-meso cells via intravenous infusion (IV).

Experimental

Subjects will receive a single dose of 1-3x10^7/m^2 lentiviral transduced huCART-meso cells on day 0 via intravenous infusion.