Adoptive Transfer of Specific HCC Antigens CD8+ T Cells for Treating Patients With Relapsed/Advanced HCC

Hepatocellular Carcinoma Clinical Trial

Official title:

A Study of Specific HCC Antigens CD8+ T Cells Therapy for Treating Patients With Relapsed/Advanced Hepatocellular Carcinoma (HCC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03175705
• Other study ID #: Beijing Youan Ethics[2017]06
• Status: Recruiting
• Phase: Phase 1
• First received: May 24, 2017
• Last updated: January 17, 2018
• Start date: May 1, 2017
• Est. completion date: March 30, 2019

Study information

• Verified date: January 2018
• Source: Beijing YouAn Hospital
• Contact: Jun Lu, Director
• Phone: 86-13661381489
• Email: lujun98[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study enrolls patients who have relapsed/advanced hepatocellular carcinoma (HCC, BCLC stage C). The HCC tumor relapsed or metastasized through the body after standard treatment or the patients cannot receive standard treatment under current conditions. This research study uses specific HCC antigens CD8+ T cells, a new experimental treatment.

The purpose of this study is to evaluate the safety and tolerance as well as the potential clinical efficacy of an adoptive transfer of CD8+ T cells, sorted with human leukocyte antigen (HLA)-peptide multimers and specific for Glypican (GPC)-3 /New York Esophageal Squamous-1 (NY-ESO-1) /alpha-fetoprotein (AFP) antigens and cultured in vitro, to patients suffering from relapsed/advanced hepatocellular carcinoma (HCC).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: March 30, 2019
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age 18-80 years

• Patients with relapsed/advanced HCC (BCLC, stage C) proved by histopathology or proved by CT or MRI imaging system, proven GPC3/NY-ESO-1/AFP(+), relapsed after previous therapy and no effective therapies known at this time.

• Life expectancy of = 12 weeks.

• WBC>3.5×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value.

• Able to understand and sign the informed consent.

Exclusion Criteria:

• Any uncontrolled systematic disease: hypertension, heart disease, and et al.;

• Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors;

• Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment;

• Unstable immune systematic diseases or Infectious diseases;

• Combined with AIDS or syphilis;

• Patients with history of stem cell or organ transplantation;

• Patients with allergic history to related drugs and immunotherapy;

• Patients with complications associated with liver diseases: moderate or severe pleural effusion, pericardial effusion, ascites, or gastrointestinal hemorrhage;

• Pregnant or lactating subjects;

• Unsuitable subjects considered by clinicians.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• HCC antigens-specific CD8+ T lymphocytes
Three different dosing schedules will be evaluated. Three patients will be evaluated on each dosing schedule. The following dose levels will be evaluated: Loading Dose 1: 3x10^7/m2 Loading Dose 2: 6x10^7/m2 Loading Dose 3: 9x10^7/m2 The doses are calculated according to the actual number of GPC3/NY-ESO-1/AFP specific cytotoxic lymphocytes (CTLs)

Drug:
• IL-2
IL-2 will be given at a dose of 25000 IU/kg/day for 5-14 days.
• Tegafur
Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.

Locations

Country	Name	City	State
China	Beijing Youan Hospital,Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing YouAn Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progress Free Survival (PFS)	PFS is the time that passes from the date that patient enrolled in the clinical trial and the date on which HCC progresses or the date on which the patient dies. HCC progression was evaluated by imaging according to the irRC standard.	12 weeks or up to death
Other	Disease Control Rate (DCR)	DCR is the proportion of patients who had a response rate including complete remission (CR), partial remission (PR) and disease stabilization (SD) evaluated by imaging according to the irRC standard.	12 weeks or up to death
Primary	Incidence of Treatment-Emergent Adverse Events [Safety]	Defined as signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2.	4 weeks
Secondary	Biological activity of infused T cells	To assess the biological activity of infused in vitro expanded and sorted HCC antigens-specific T cells.	4 weeks