Clinical Safty and Efficacy Study of Infusion of iNKT Cells and CD8+T Cells in Patients With Advanced Solid Tumor

Non-small Cell Lung Cancer Clinical Trial

Official title:

Phace I and II Study of Immunotherapy Strategy Used iNKT Cells and CD8+T Cells in Patients With Advanced Tumor

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03093688
• Other study ID #: iNKT20170215V1.2
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2017
• Est. completion date: June 30, 2023

Study information

• Verified date: May 2022
• Source: Shanghai Public Health Clinical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Invariant Natural killer T (iNKT) cells are a unique subset of lymphocytes that express homogeneous TCR recognizing KRN7000 which was up-regulated by many kinds of cancer cells. PD-1+CD8+T cells of patients with advanced tumor are most likely tumor-specified. Our hypothesis is that immunotherapy strategy of infusion of iNKT cells and PD-1+CD8+T cells may decrease the tumor burden and improve overall survival. The purpose of this study is to assess the safety and efficacy of treatment of patients with advanced solid tumor by infusing of iNKT cells and PD-1+CD8+T cells.

Description:

Treatment of patients with advance solid tumor is great unsolved challenge to the physicians. Efficacy of conventional treatment, such as surgery, radiotherapy and chemotherapy is limited. AS novel therapy, immunotherapy shows great prospects.

Human iNKT cells can directly lysis tumor cells by a perforin-dependent mechanism,and intracellular granzyme B expression may also potentiate cell killing. Tumor cells expressing CD1d may be especially susceptible to direct NKT cell lysis. iNKT cells play important role in immune regulation by secreting various cytokines. PD-1+CD8+T cells are most likely tumor-specific in patient with advanced tumor. Expansion method of iNKT cells and PD-1+CD8+T cells in vitro is developed as published in our patent. Infusions of iNKT cells and CD8+T cell have been proved safe in mice.

In this clinical trial, the safety and efficacy of the immunotherapy of infusion of iNKT cells and CD8+T cells are assessed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: June 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Histological or cytologically diagnosis of advanced lung cancer, or advanced gastric cancer, or advanced pancrease cancer, or hepatocellular carcinoma, or advanced colorectal cancer

• Patients' tumor tissue (formalin-fixed, paraffin-embedded) must be sufficient for diagnosis of cancer by a certified Laboratory of Pathology

• Laboratory values within the following ranges prior to receiving treatment of study agent: Hemoglobin?8.0 g/dL, Neutrophils count?1E9/L, Lymphocytes count?lower limit of institutional normal, Platelet count?50E9/L, Serum creatinine?2.0 mg/dL, Serum bilirubin?2 x upper limit of institutional normal, AST/ALT?2 x upper limit of institutional normal

• No dyspnea at rest. Oxygen saturation =90% on room air

• No genetic disease

• Fertile females/males must consent to use contraceptives during participation of the trial. Women of child bearing potential must have a negative pregnancy test prior to receiving treatment of study agent within 7 days

• Patients must have a Karnofsky performance status greater than or equal to 80%

• Able and willing to give witnessed, written informed consent form prior to receiving any study related procedure

• Agrees to participate in long-term follow-up for up to 1 years, if received NKT infusion

Exclusion Criteria:

• Organ dysfunction,such as significant cardiovascular disease, myocardial infarction within the past six months, unstable angina, coronary angioplasty within the past six months, uncontrolled atrial or ventricular cardiac arrhythmias; Child-Pugh C; Renal function failure or uremia; Respiratory failure; Disturbance of consciousness; Renal failure.

• Suffering from lymphoma or leukemia

• Serious infections requiring antibiotics, bleeding disorders

• Patients with myelodysplastic syndrome (MDS)

• History of immunodeficiency disease or autoimmune disease

• Positive HIV antigen and antibody, Hepatitis B surface antigen and Hepatitis C PCR within 21 days prior to enrollment

• Within concurrent chemotherapy

• Concurrent other medical condition that would prevent the patient from undergoing protocol-based therapy

• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent

• Pregnant or breast-feeding patients

• Can't give informed consent

• Lack of availability for follow-up assessment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Gastric Cancer
• Hepatocellular Carcinoma
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Pancreas Cancer
• Pancreatic Neoplasms
• Renal Cell Carcinoma
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Biological:
• Infusion of iNKT cells and CD8+T cells
The eligible patients receive twice infusions of iNKT cells(1E8~1E10) and CD8+T cells(1E7~1E9) in one course of treatment.

Locations

Country	Name	City	State
China	Shanghai Public Health Clinical Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Public Health Clinical Center

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression-Free Survival (PFS)	Progression-Free Survival (PFS)	Approximately 1 years after the treatment
Primary	Incidence of adverse events related to the infusion of cells	The incidence of adverse events following infusion of iNKT cells and CD8+T cells	28 days post-infusion
Primary	Objective Response Rate (ORR)	Change of target focus confirmed by CT or MRI	up to 4 months post-infection
Secondary	Hematologic analysis	Hematologic analysis is used to assess the impact of infusion to the cells in blood, including erythrocytes, leukocytes, platelets, T lymphocytes , B lymphocytes, Natural killer cell, NKT, CD4/CD8, and Treg lymphocytes.	Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
Secondary	Liver biochemical examination	Liver Biochemical examination is a serological analysis about the metabolites related to the function of liver , such as immunoglobulins, Albumin (ALB), Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), Prealbumin (PA), total bilirubin (TB), and direct bilirubin (DB).	Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
Secondary	Kidney biochemical examination	Kidney Biochemical examination is a serological analysis about the metabolites related to the function of liver, such as Blood urea nitrogen (BUN), Urea (UA), and Crea (Cr).	Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
Secondary	Tumor Marker	Tumor Marker	Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment