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

Primary Purpose

Non-small Cell Lung Cancer, Small Cell Lung Cancer, Pancreas Cancer

Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Infusion of iNKT cells and CD8+T cells
Sponsored by
Shanghai Public Health Clinical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Shanghai Public Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment

Arm Description

The eligible patient receive the experimental infusion of iNKT cells and CD8+T cells .

Outcomes

Primary Outcome Measures

Incidence of adverse events related to the infusion of cells
The incidence of adverse events following infusion of iNKT cells and CD8+T cells
Objective Response Rate (ORR)
Change of target focus confirmed by CT or MRI

Secondary Outcome Measures

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.
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).
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).
Tumor Marker
Tumor Marker

Full Information

First Posted
March 15, 2017
Last Updated
May 6, 2022
Sponsor
Shanghai Public Health Clinical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03093688
Brief Title
Clinical Safty and Efficacy Study of Infusion of iNKT Cells and CD8+T Cells in Patients With Advanced Solid Tumor
Official Title
Phace I and II Study of Immunotherapy Strategy Used iNKT Cells and CD8+T Cells in Patients With Advanced Tumor
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Public Health Clinical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer, Small Cell Lung Cancer, Pancreas Cancer, Hepatocellular Carcinoma, Gastric Cancer, Renal Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
treatment group: receive twice cell infusions in one course of treatment.
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
treatment
Arm Type
Experimental
Arm Description
The eligible patient receive the experimental infusion of iNKT cells and CD8+T cells .
Intervention Type
Biological
Intervention Name(s)
Infusion of iNKT cells and CD8+T cells
Intervention Description
The eligible patients receive twice infusions of iNKT cells(1E8~1E10) and CD8+T cells(1E7~1E9) in one course of treatment.
Primary Outcome Measure Information:
Title
Incidence of adverse events related to the infusion of cells
Description
The incidence of adverse events following infusion of iNKT cells and CD8+T cells
Time Frame
28 days post-infusion
Title
Objective Response Rate (ORR)
Description
Change of target focus confirmed by CT or MRI
Time Frame
up to 4 months post-infection
Secondary Outcome Measure Information:
Title
Hematologic analysis
Description
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.
Time Frame
Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
Title
Liver biochemical examination
Description
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).
Time Frame
Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
Title
Kidney biochemical examination
Description
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).
Time Frame
Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
Title
Tumor Marker
Description
Tumor Marker
Time Frame
Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
Other Pre-specified Outcome Measures:
Title
Progression-Free Survival (PFS)
Description
Progression-Free Survival (PFS)
Time Frame
Approximately 1 years after the treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qing J Xu, M.D. Ph.D
Organizational Affiliation
Shanghai Public Health Clinical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Shanghai Public Health Clinical Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201508
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35367396
Citation
Cheng X, Wang J, Qiu C, Jin Y, Xia B, Qin R, Hu H, Yan J, Zhang X, Xu J. Feasibility of iNKT cell and PD-1+CD8+ T cell-based immunotherapy in patients with lung adenocarcinoma: Preliminary results of a phase I/II clinical trial. Clin Immunol. 2022 May;238:108992. doi: 10.1016/j.clim.2022.108992. Epub 2022 Mar 30.
Results Reference
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Clinical Safty and Efficacy Study of Infusion of iNKT Cells and CD8+T Cells in Patients With Advanced Solid Tumor

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