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

May 6, 2022 updated by: Xiaoyan Zhang, Shanghai Public Health Clinical Center

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201508
        • Shanghai Public Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: treatment
The eligible patient receive the experimental infusion of iNKT cells and CD8+T cells .
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: up to 4 months post-infection
Change of target focus confirmed by CT or MRI
up to 4 months post-infection
Incidence of adverse events related to the infusion of cells
Time Frame: 28 days post-infusion
The incidence of adverse events following infusion of iNKT cells and CD8+T cells
28 days post-infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematologic analysis
Time Frame: Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
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
Liver biochemical examination
Time Frame: Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
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
Kidney biochemical examination
Time Frame: Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment
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
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
Tumor Marker
Base line, the day before the first infusion in each course of treatment and up to 12 weeks after the treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Approximately 1 years after the treatment
Progression-Free Survival (PFS)
Approximately 1 years after the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Public Health Clinical Center

Investigators

  • Study Chair: Qing J Xu, M.D. Ph.D, Shanghai Public Health Clinical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 1, 2017

Primary Completion (ANTICIPATED)

December 31, 2022

Study Completion (ANTICIPATED)

June 30, 2023

Study Registration Dates

First Submitted

March 15, 2017

First Submitted That Met QC Criteria

March 22, 2017

First Posted (ACTUAL)

March 28, 2017

Study Record Updates

Last Update Posted (ACTUAL)

May 9, 2022

Last Update Submitted That Met QC Criteria

May 6, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • iNKT20170215V1.2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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