NewishT Cell Therapy for HCC With High Risk of Recurrence After Radical Resection
Study Details
Study Description
Brief Summary
This is a single-arm, open label, multi-center Phase 1 clinical study to evaluate the safety and efficacy of autologous memory lymphocyte therapy (NewishT) in patients with hepatocellular carcinoma at high risk of recurrence after radical resection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study is divided into two dose groups and two phases. Phase Ia climbed from low-dose group to high-dose group in turn according to the 3+3 dose escalation principle. Phase Ib extended 10 subjects each group.
After the completion of treatment, the subjects shall continue to receive safety follow-up until 14 days after the last administration, and all adverse events shall revert to level I or all adverse events shall be clinically stable (whichever is later achieved); Tumor imaging assessment was performed at week 7 and week 20 to observe the progression of disease.
After week 20, the survival follow-up period was entered, and patients were followed up until death, loss of follow-up, or trial termination, whichever occurred first. Survival was followed up by telephone every 12 weeks (±7 days), and radiographic evidence should be obtained if recurrence/progression occurred.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NewishT This study is divided into two dose groups and two phases. Phase Ia climbed from low-dose group to high-dose group in turn according to the 3+3 dose escalation principle. Phase Ib extended 10 subjects each group. |
Drug: Autologous memory lymphocyte Injection (NewishT), low-dose group
Recruited participants in low-dose group will receive autologous memory lymphocyte (NewishT) intravenous infusion every 4 weeks, a total of 2 times.
Other Names:
Drug: Autologous memory lymphocyte Injection (NewishT), high-dose group
Recruited participants in high-dose group will receive autologous memory lymphocyte (NewishT) intravenous infusion every 2 weeks, a total of 4 times.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- dose-limiting toxicity (DLT) [14 days after last administration]
Any AEs that is definitely, probably, or possibly related to the test drug occurring within 14 days of the last dosing will be classified as DLT during dosing climb.
Secondary Outcome Measures
- All adverse events (AE) [1 year]
Including incidence and severity of serious adverse events (SAE) (according to NCI-CTCAE Standard version 5.0 of common Terms for Adverse Events)
- recurrence-free survival(RFS) rate [1 year]
The probability of no recurrence or death within 1 year from the date of radical hepatocellular carcinoma resection.
Eligibility Criteria
Criteria
The inclusion criteria
Patients must meet all of the following inclusion criteria:
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18≤ age ≤75 years, no gender limitation;
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Primary hepatocellular carcinoma (HCC) confirmed by histopathological examination;
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Serological tests were positive for HBsAg or HBV DNA, and patients with active virus were willing to receive anti-HBV therapy during the study period;
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Barcelona Clinic liver cancer (BCLC) stage A/B or CNLC stage IIA-IIIA;
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Radical hepatocellular carcinoma surgery (laparotomy, laparoscopic surgery, ablation, robot-assisted surgery) was performed within 12 weeks before blood collection for the first preparation of NewishT; The interval between clinical stage determination of BCLC or CNLC liver cancer and radical resection is no more than 12 weeks.
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No residual tumor was found in liver during image examination within 4 weeks before blood collection for the first NewishT preparation; No lymph node metastasis, no extrahepatic metastasis;
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Have not received systematic anti-tumor therapy for liver cancer (including chemotherapy, molecular targeted therapy, biological immunotherapy, and proprietary Chinese medicines with clear indications for liver cancer);
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Patients undergoing radical surgery should meet the intraoperative judgment criteria of radical surgery for liver cancer:
(1) No gross tumor thrombus was found in hepatic vein, portal vein, bile duct and inferior vena cava during operation (including preoperative imaging examination). (2) There were no intrusions of adjacent organs, hilar lymph nodes or distant metastasis during operation (including preoperative imaging examination). (3) The incisal margin was negative.
(9) Meeting any of the following high recurrence risk factors after radical surgery: Patients undergoing radical surgery :(1) the number of tumors ≥3; (2) Single tumor patients: patients with tumor diameter ≥ 5cm; (3) Single tumor: microvascular invasion (MVI) was found in patients with tumor diameter < 5cm. (4) Edmondson-Steiner grade ⅲ or ⅳ for hepatocellular carcinoma; Patients undergoing radical ablation: (1) Patients with multiple tumors: the diameter of all tumors ≤5cm, and the number of tumors ≤4; (2) Single tumor patients: tumor diameter 2-5cm; (3) Edmondson-Steiner grading of hepatocellular carcinoma was grade ⅲ or ⅳ.
(10) ECOG fitness state score was 0~1 in 1 week before blood collection for the first NewishT preparation; (11) Child-Pugh score A/B (≤7 points) within 1 week before blood collection for the first NewishT preparation; (12) The main organ functions were normal within 1 week before blood collection for the first NewishT preparation:
Blood routine:
Hemoglobin (Hb) ≥75 g/L (no erythrocyte concentration infusion or erythropoietin use within 2 weeks); Neutrophil absolute count (ANC) ≥1.5×109/L (no granulocyte colony stimulating factor was used within 2 weeks); Absolute lymphocyte count (LYMP) ≥0.8×109/L; Platelet count (PLT) ≥75×109/L;
The liver:
Total bilirubin (TB) ≤3× upper normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN; plasma albumin ≥28g/L;
Coagulation function:
International standardized ratio (INR) ≤2.3;
Kidney:
Serum creatinine (Scr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min (serum creatinine & GT; 1.5 x ULN); (13) The expected survival time is more than 6 months; (14) Within 1 week before blood collection for the first preparation of NewishT, women of childbearing age must have a negative serum pregnancy test and consent to use effective contraception during the study drug use and for 6 months after the last administration of the study drug. For men, surgical sterilization or consent to use effective contraception during the study drug use period and for six months after the last administration of the study drug.
(15) Have fully understood the study and voluntarily signed the ICF, have good communication with the researcher and can complete all the treatment, examination and visit required by the study protocol.
Exclusion criteria
Patients with any of the following conditions cannot be enrolled in this study:
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HCC recurred before blood collection for the first NewishT preparation;
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The toxicity and/or complications of radical surgery were not fully recovered before blood collection for the first preparation of NewishT;
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Contraindications to TACE;
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After radical hepatectomy or during the screening period, patients have received or are going to receive radiotherapy, chemotherapy, molecular targeted therapy, biotherapy, TACE therapy, radiofrequency ablation and other anti-liver cancer treatments (except postoperative TACE adjuvant therapy as specified in the protocol);
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hepatic encephalopathy;
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Regular renal dialysis is required;
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with uncontrolled pleural effusion, pericardial effusion, or ascites of medium or above volume (refers to ascites that cannot be easily controlled by diuretic treatment);
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Have a history of gastrointestinal bleeding within 28 days before screening, or have active bleeding at present, or have bleeding tendency;
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Have received liver tumor radiotherapy, microwave ablation, cryotherapy, high-power ultrasound focused ablation and other local treatments, except radical ablation or surgery;
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Participating in other clinical trials or in the observation period of other clinical trials within 28 days prior to screening;
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continuous glucocorticoid treatment (dose equivalent to prednisone & GT) for more than 1 week within 28 days prior to screening; 10 mg/ day), except for hormone replacement therapy and intratracheal administration;
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have a history of immune deficiency or autoimmune diseases (such as rheumatoid joint disease, systemic lupus erythematosus, multiple sclerosis, etc.);
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History of allogeneic stem cell/tissue/solid organ transplantation (including bone marrow transplantation);
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with uncontrolled severe infection (> Level 2 NCI-CTC adverse events, version 5.0);
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have a history of hepatitis C virus (HCV) infection or human immunodeficiency virus (HIV) infection or syphilis carriers;
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patients with serious other organ dysfunction or cardiopulmonary diseases, including myocardial infarction, stroke, congestive heart failure, severe lung disease, metabolic diseases, wound healing abnormalities, ulcers or fractures, etc.;
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accompanied by epilepsy requiring medication (e.g. steroids or antiepileptic drugs);
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have previously or currently have other malignancies (except for adequately treated and complete ductal carcinoma in situ of the breast, carcinoma in situ of the cervix, basal cell carcinoma of the skin, superficial bladder, or any malignancy that has been cured for more than 5 years prior to entry into the study);
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have a known history of albumin allergy, or a history of severe allergy, or a history of allergic disease, or an allergic constitution, or a history of severe iodine contrast agent allergy, meeting any of these criteria;
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serious mental disorders;
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have a history of drug abuse or alcohol abuse;
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women who are pregnant or lactating, or women of childbearing age who have positive blood pregnancy tests, or patients of childbearing age and their spouses are unwilling to use effective contraception during and for 6 months after the clinical study;
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Patients considered unsuitable for the clinical trial by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer Hospital, Chinese Academy of Medical Sciences | Beijing | China |
Sponsors and Collaborators
- Newish Technology (Beijing) Co., Ltd.
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Investigators
- Principal Investigator: Jianqiang Cai, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NewishT-HCC-002