Clinical trial NCT05268172: IFN-γ Combined With T Cells in the Treatment of Refractory Malignant Pleural Effusion and Ascites
Official title: Single-arm Open Multicenter Study of IFN-γ Combined With T Cells in the Treatment of Refractory Malignant Pleural Effusion Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pleural Effusion, Malignant
Lead sponsor: Affiliated Hospital of Jiangnan University
Sponsor class: OTHER
Collaborators: name: Sichuan University
name: Zhejiang Provincial People's Hospital
name: Hunan Cancer Hospital
name: West China Hospital
name: Wuxi People's Hospital
name: Shenzhen Second People's Hospital
First posted: 2022-03-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Puncture-free Survival (PuFS)
timeFrame: Focusing on the time from the end of the T Cells treatment procedure to the next required drainage or death
Secondary outcomes:
measure: Disease control rate
timeFrame: The tumor shrinks or stabilizes for a certain period of time，Lasts at least 4 weeks
measure: Objective response rate
timeFrame: 8 weeks
measure: Molecular markers for efficacy prediction
timeFrame: 8 weeks
measure: Overall survival
timeFrame: 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
measure: Progression-free survival
timeFrame: From time of treatment to time of disease progression or death from any cause as assessed by the investigator at each treatment period
Other outcomes:
Locations:
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
Study officials:
affiliation: Affiliated Hospital of Jiangnan University
name: quan liu, doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Affiliated Hospital of Jiangnan University
name: liu quan, doctor
role: STUDY_DIRECTOR
References: