IFN-γ Combined With T Cells in the Treatment of Refractory Malignant Pleural Effusion and Ascites

Single-arm Open Multicenter Study of IFN-γ Combined With T Cells in the Treatment of Refractory Malignant Pleural Effusion Tumors

The purpose of this study was to evaluate the efficacy of IFN- Y combined with T cells in the treatment of refractory malignant pleural effusion and acties, using a multicenter, single-arm, open design.

Study Overview

• Status: Recruiting
• Conditions: Pleural Effusion, Malignant
• Intervention / Treatment: Drug: IFN-γ and CIK cells, Tcm cells or CAR T cells

Detailed Description

Malignant pleural effusion is a common complication of malignant tumor, which usually indicates that the patient has reached the advanced stage, and about 30-40% of the patients are stubborn and refractory cases. The lack of standard therapeutic drugs and protocols in clinical practice seriously affects the anti-tumor treatment effect, quality of life and survival time of patients, and the prognosis is poor. IFN-γ can significantly induce the high expression of the costimulatory molecule ICAM-1 on tumor cells, thereby enhancing the killing of TUMOR cells by T cells. Moreover, IFN-γ can enhance the activity of CAR T cells in the presence of PD-L1-PD-1 pathway, and significantly improve the therapeutic effect of T cells on solid tumors. IFN-γ is an approved clinical treatment with known side effects and well-established symptomatic treatment. Although CIK is not a clinically approved drug, it has been used on a large scale in China with good safety and has entered the medical insurance of some provinces and cities. Tcm is an improved CIK cell and has good safety. Many clinical studies have been carried out, and no serious toxic and side effects have been observed.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: liu quan, doctor; Phone Number: 15995299079; Email: Quanliu.lq@outlook.com
• Study Contact Backup: Name: jiang li qing, postgraduate; Phone Number: 15261479578; Email: jjiangliq@163.com

Study Locations

• China
  • Jiangsu
    • Wuxi, Jiangsu, China, 214000
      • Recruiting
      • Affiliated Hospital Of Jiangnan University
      • Contact: 劝 刘; Phone Number: 15995299079

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients: ≥18 years old;
2. Gastric cancer, colon cancer, lung cancer, lymphoma and other tumors confirmed by histology or cytology. The guidelines recommend entry to clinical trials in accordance with the standard treatment progression recommended by each disease guideline;
3. According to iRECIST criteria, the patient should have at least one target lesion with measurable diameter line (tumor lesion CT scan length ≥10 mm, lymph node lesion CT scan short diameter ≥15 mm, scan thickness ≥ 5 mm); Or an unevaluable lesion, including but not limited to pleural effusion, bone metastasis, etc;
4. ECOG physical condition score: 0-3;
5. Estimated survival ≥3 months;
6. Good function of major organs, that is, relevant examination indexes within the first 14 days of randomization meet the following requirements:(1)Routine blood test: 1)Hemoglobin ≥ 90 g/L (no blood transfusion within 14 days); 2)Neutrophil count > 1.5×109/L; 3)Platelet count ≥ 90×109/L; (2)Biochemical examination: 1)Total bilirubin ≤ 1.5×ULN (upper limit of normal value); 2)Serum alanine aminotransferase (ALT) or AST ≤ 2.5×ULN; ALT or AST ≤ 5×ULN if liver metastasis was present; 3)Endogenous creatinine clearance ≥ 60 mL /min (Cockcroft-Gault formula); (3)Cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%;
7. Signed informed consent;
8. Good compliance, family members agreed to cooperate with survival follow-up.

Exclusion Criteria:

1. Participated in clinical trials of other drugs within four weeks;
2. Patients have a history of other tumors, except cervical carcinoma in situ, treated squamous cell carcinoma or bladder epithelial tumor (Ta and TIS), or other malignant tumors that have received radical treatment (at least 5 years prior to enrollment);
3. Patients with cardiac clinical symptoms or diseases that are not well controlled, such as NYHA grade 2 or above heart failure, unstable angina pectoris, myocardial infarction within 1 year, and clinically significant ventricular or ventricular arrhythmias requiring treatment or intervention；
4. For female subjects: surgically sterilized, postmenopausal, or have agreed to use a medically approved contraceptive during study treatment and for 6 months after the study treatment period; Serum or urine pregnancy tests must be negative during the 7 days prior to study enrollment and must be non-lactation. Male subjects: patients who are surgically sterilized or who have agreed to use a medically approved contraceptive during and for 6 months after the study treatment period；
5. Patients with active tuberculosis, bacterial or fungal infection (grade ≥2 of NCI-CTC, 3rd edition); Have HIV infection, HBV infection, HCV infection；
6. Those who have a history of psychotropic drug abuse and cannot get rid of it or have mental disorders;
7. The subject has any active autoimmune disease or a history of autoimmune disease (e.g., but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism); Subjects with vitiligo or asthma in complete remission during childhood without any intervention as adults could be included; Subjects with asthma requiring medical intervention with bronchodilators were excluded)；
8. According to the judgment of the researcher, there are serious concomitant diseases that endanger the patient's safety or affect the patient's ability to complete the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IFN- Y combined with T cells; First, IFN-γ was combined with CIK cells. After three failed treatments, the CIK cells were replaced with T cells. After three failed treatments, CART cells were finally replaced.

Drug: IFN-γ and CIK cells, Tcm cells or CAR T cells; A 50ng/ mL IFN-γ solution was prepared, and the required volume of IFN-γ solution was calculated according to the final concentration of 5ng/ mL according to the volume of pleural fluid or ascites of the patient. CIK cells were injected 1.0-2.0×109 on the second day and review three days later.T cells and CAR T cells were selected sequentially according to the re-examination of pleural fluid or ascites.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The last follow-up time of the lost patient; Patients who were still alive at the end of the study were at the end of follow-up	From the time of diagnosis of tumor to death from any cause，From initiation of study treatment until date of death from any cause, up to 100 months
Progression-free survival	From time of treatment to time of disease progression or death	From time of treatment to time of disease progression or death from any cause as assessed by the investigator at each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	Proportion of patients who had a best response rating of complete response, partial response, or stable disease	The tumor shrinks or stabilizes for a certain period of time，Lasts at least 4 weeks
Objective response rate	Total response and partial response ratio	8 weeks
Molecular markers for efficacy prediction	Prediction effect	8 weeks

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Jiangnan University
• Collaborators: West China Hospital; Hunan Cancer Hospital; Shenzhen Second People's Hospital; Zhejiang Provincial People's Hospital; Wuxi People's Hospital; Sichuan University
• Investigators: Principal Investigator: quan liu, doctor, Affiliated Hospital Of Jiangnan University; Study Director: liu quan, doctor, Affiliated Hospital Of Jiangnan University

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion
• Other Study ID Numbers: 1362566548

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The associated efficacy is uncertain

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No