Study on TIL for the Treatment of Advanced Hepatobiliary-Pancreatic Cancers
Study Details
Study Description
Brief Summary
This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with advanced hepatobiliary-pancreatic cancers. Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with fludarabine and cyclophosphamide.
Condition or Disease | Intervention/Treatment | Phase |
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Early Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Tumor Infiltrating Lymphocytes 1x10^9-5x10^10 in vitro expanded autologous TILs will be infused i.v. to patients with advanced hepatobiliary-pancreatic cancers after NMA lymphodepletion treatment with fludarabine and cyclophosphamide. |
Biological: Tumor Infiltrating Lymphocyte
Adoptive transfer of 1x10^9-5x10^10 autologous TILs to patients i.v. in 30-120 minutes.
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Outcome Measures
Primary Outcome Measures
- Adverse Events (AE) [up to 6 months]
To characterize the safety profile of GC101 TIL in patients with advanced hepatobiliary-pancreatic cancers as assessed by incidence of adverse events.
- Objective Response Rate (ORR) [up to 36 months]
Proportion of patients with response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): ORR (proportion of patients) = # with CR + # with PR / # with CR + # with PR + # with SD + # with PD. ( Except baseline evaluation within 28 days before TIL infusion,PET/CT scan will be performed at 6 weeks after TIL infusion, and than every 6 weeks for 6 months, and then every 6 months after that for up to 3 years)
- Disease Control Rate (DCR) [Up to 36 months]
Percentage of patients that meet CR, PR and SD criteria set in this study according to RECIST v1.1: DCR (proportion of patients) = # with CR + # with PR + # with SD / # with CR + # with PR + # with SD + # with PD.
- Duration of Response (DOR) [Up to 36 months]
The time length between the first confirmed objective response per RECIST 1.1 to the GC101 TIL treatment and the subsequent disease progression per RECIST 1.1
- Progression-Free Survival (PFS) [Up to 36 months]
The time length between GC101 TIL infusion and confirmed subsequent disease progression according to RECIST 1.1
- Overall Survival (OS) [Up to 36 months]
The length of time from the date of the start of GC101 TIL treatment that the patients are still alive.
Secondary Outcome Measures
- Change in Quality of Life [Up to 36 months]
Comparison of patients' quality of life before and after GC101 TIL treatment as assessed by the EORTC QLQ-30 (V3.0).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age: 18 years to 75 years;
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Histologically diagnosed as primary/relapsed/metastasized hepatobiliary cancer or pancreatic cancers;
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Expected life-span more than 3 months;
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Karnofsky≥60% or ECOG score 0-2;
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Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
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Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;
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At least 1 evaluable tumor lesion;
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Hematology and Chemistry(within 7 days prior to enrollment):
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Absolute count of white blood cells≥2.5×10^9/L;
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Absolute count of neutropils≥1.5×10^9/L;
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Absolute count of lymphocytes ≥0.7×109/L;
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Platelet count≥100×10^9;
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hemoglobin≥90 g/L;
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Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
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International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
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Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min;
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Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN);
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Totol bilirubin≤1.5×ULN;
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no absolute or relative contraindications to operation or biopsy;
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Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion;
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Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs;
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Be able to understand and sign the informed consent document;
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Be able to stick to follow-up visit plan and other requirements in the agreement.
Exclusion Criteria:
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Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;
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Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;
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Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.
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Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;
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Severe physical or mental diseases;
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Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);
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Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
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History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;
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Having received immunotherapy and developed irAE level greater than Level 3;
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Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);
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Females in pregnancy or lactation;
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History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;
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Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Shanghai Tenth People's Hospital | Shanghai | Shanghai | China | 200000 |
Sponsors and Collaborators
- Shanghai Juncell Therapeutics
- Shanghai 10th People's Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GC-101-21K145