Clinical Research on Comprehensive Treatment of Tuberculosis With Malignant Solid 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.The hypothesis of the investigators is that immunotherapy strategy of infusion of iNKT cells may resist inflection and decrease the tumor burden and improve overall survival. The purpose of this study is to assess the safety and efficacy of treatment of tuberculosis with malignant solid tumor by infusing of iNKT cells.

Study Overview

• Status: Completed
• Conditions: Malignant Solid Tumor
• Intervention / Treatment: Biological: Infusion of iNKT cells

Detailed Description

Treatment of tuberculosis with malignant 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. Expansion method of iNKT cells in vitro is developed as published in the patent of the investigators. Infusion of iNKT cells has been proved safe in mice.

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

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological or cytologically diagnosis of tuberculosis with malignant solid tumor
• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: treatment; The eligible patient receive the experimental infusion of iNKT cells.	Biological: Infusion of iNKT cells; The eligible patients receive twice infusions of iNKT cells(1E8~1E10) in one course of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Change of target focus confirmed by CT or MRI	up to 4 months post-infection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events related to the infusion of cells	The incidence of adverse events following infusion of iNKT cells	28 days post-infusion

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Xiaoyan Zhang
• Investigators: Study Chair: Qing J Xu, Ph.D, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Jin Shan, Shanghai 201508, P.R. China

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ACTUAL): December 30, 2021
• Study Completion (ACTUAL): March 31, 2022

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 28, 2018
• First Posted (ACTUAL): June 11, 2018

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: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Neoplasms; Tuberculosis
• Other Study ID Numbers: iNKT20180427V1.1

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