Study of Autologous CIK Cell Immunotherapy Combination With PD-1 Inhibitor and Chemotherapy in the Advanced NSCLC

NCT ID: NCT03987867

Last Updated: 2020-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-01
• Study Completion Date: 2021-06-01

Brief Summary

This prospective, unicentric, open-labe phase I study is to evaluate the effects of autologous cytokine-induced killer cell immunotherapy combination with PD-1 inhibitor and chemotherapy in the first-line treatment of IIIB/IIIC/IV non-small cell lung cancer.

Detailed Description

In the non-squamous NSCLC, patients received sintilimab Injection (PD-1 inhibitor) 200mg, d1; pemetrexed injection 500mg/m2, d1; carboplatin injection AUC 5, d1; CIK cells venous re-transfusion >=1x10^10, d14; Q3W, for 4 cycles. Then sintilimab and pemetrexed maintenance treatment for 2 years. In the squamous NSCLC, patients received sintilimab Injection (PD-1 inhibitor) 200mg, d1; liposome paclitaxel injection 135mg/m2, d1; carboplatin injection AUC 5, d1; CIK cells venous re-transfusion >=1x10^10, d14; Q3W, for 4 cycles. Then sintilimab maintenance treatment for 2 years.

Conditions

Non-small Cell Lung Cancer; First-line Treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm: CIK+PD-1 inhibitor+chemotherapy

CIK cell, IBI308, Pemetrexed, Liposome paclitaxel, Carboplatin

IBI308 intravenous infusion 200mg d1; Pemetrexed intravenous infusion 500mg/m2 d2 or Liposome paclitaxel intravenous infusion 135mg/m2 d2; Carboplatin intravenous infusion AUC5 d2; CIK cells, 1x10^10 (10 billion ), intravenous infusion,d14; Q3W.

Group Type: EXPERIMENTAL

CIK cell

Intervention Type: BIOLOGICAL

CIK cell injection

Sintilimab Injection

Intervention Type: BIOLOGICAL

IBI308 injection

Pemetrexed

Intervention Type: DRUG

Pemetrexed injection

Liposome paclitaxel

Intervention Type: DRUG

Liposome paclitaxel injection

Carboplatin

Intervention Type: DRUG

Carboplatin injection

Interventions

CIK cell

CIK cell injection

Intervention Type: BIOLOGICAL

Sintilimab Injection

IBI308 injection

Intervention Type: BIOLOGICAL

Pemetrexed

Pemetrexed injection

Intervention Type: DRUG

Liposome paclitaxel

Liposome paclitaxel injection

Intervention Type: DRUG

Carboplatin

Carboplatin injection

Intervention Type: DRUG

Other Intervention Names

Autologous cytokine-induced killer cells; PD-1 inhibitor

Eligibility Criteria

Inclusion Criteria

Subjects who must meet all the following criteria should be selected:

1. Agreeing to participate in this study and signing a written informed consent.

2. Male or female,from 18 to 75 years (including 18 and 75 years).

3. The life expectancy will be longer than 3 months and can be followed up.

4. Patients with stage IIIB/IIIC/IV NSCLC were confirmed by histological /cytological and imaging examinations. According to RECIST 1.1 standard, there will be at least one measurable lesion.

5. Initial medical treattment.Patients with adenocarcinoma need wild type of EGFR gene and ALK fusion gene negative to be included in this study.

6. ECOG score will be 0 or 1 within 7 days before randomization.

7. Within 14 days before the start of treatment, the results of laboratory test of blood routine, liver, kidney function and hormone levels must be met the following criteria:

White blood cells: more than 3.0 × 109/L; Platelets: more than 100 × 109/L; Neutrophils: more than 1.5 × 109/L; Hemoglobin: more than 80g/L; Serum glutamate pyruvate transaminase: less than 2.5 folds of the upper normal limit (ULN); Serum glutamic-oxal (o) acetic transaminase: less than 2.5 × ULN; Serum bilirubin: less than 1.25 × ULN; Serum creatinine: less than 1.25 × ULN. Cortisol and thyroid function will be in the normal range.

8. The toxicity and side effects of previous chemotherapy will must be alleviated to grade 1 or below (except hair loss).

9. Female subjects must take effective contraceptive measures throughout the study period; serum or urine pregnancy test results must be negative during screening and the whole study period.

10. Male subjects should take effective contraceptive measures from the beginning of treatment to within 6 months after the end of treatment.

Exclusion Criteria

Subjects who meet any of the following criteria could not participate in this study:

1. Adenocarcinoma subjects with EGFR sensitive mutation or ALK translocation; molecular detection of EGFR-sensitive mutations or ALK translocations is not required in squamous carcinoma patients.

2. NSCLC that had received chemotherapy in the past.

3. Other malignant tumors needed treatment within five years.

4. Allogeneic tissue/organ transplantation.

5. Participating in research drug therapy within 4 weeks before the first administration of the trial.

6. Systemic glucocorticoid therapy or any other form of immunosuppressive therapy (except glucocorticoid preconditioned with docetaxel) is being administered within 3 days before the first administration of the experimental therapy.

7. Received anti-tumor monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy or major surgery within 4 weeks before the first use of the drug; received chest radiotherapy greater than 30 Gy within 6 months before the first use of the drug; and received chest radiotherapy with 30 Gy or less within 1 month before the first use of the drug.

8. Previous treatment with PD-1/PD-L1 antibodies.

9. Over the past two years, patients with active autoimmune diseases requiring systemic treatment, such as the use of corticosteroids, or immunosuppressants. Substitution therapy (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary dysfunction) is not a systemic treatment.

10. Patients with congenital or acquired immunodeficiency (e.g. HIV-infected persons), active hepatitis B (HBV-DNA > 10^3 copies/ml) or hepatitis C (hepatitis C antibody positive), and HCV-RNA higher than the detection limit of the analytical method.

11. Subjects with active central nervous system (CNS) metastases and/or cancerous meningitis.

12. Patients with active infections requiring systemic intravenous therapy.

13. Mental illness or other illnesses, such as uncontrollable heart disease or pulmonary disease, diabetes, etc.

14. Subjects who are known to be allergic to any of the constituents of the drug being studied.

15. Subjects with a recent history of drug abuse (including alcohol) within one year.

16. Compliance is poor and can not cooperate with clinical research.

17. Female subjects who are pregnant or breastfeeding, or who are expected to be pregnant during the trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiubao Ren, MD. PhD.

Role: STUDY_CHAIR

Tianjin Medical University Cancer Institute and Hospital

Locations

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiubao Ren, MD. PhD.

Role: CONTACT

liangcoh@163.com

86-22-23340123 ext. 3173

Liang Liu, MD. Ph.D

Role: CONTACT

renxiubao@tjmuch.com

86-22-23340123 ext. 3172

Facility Contacts

Liang Liu, MD. Ph.D

Role: primary

liangcoh@163.com

86-22-23340123 ext. 3172

Xiubao Ren, MD. PhD.

Role: backup

renxiubao@tjmuch.com

86-22-23340123 ext. 3173

References

Zhou L, Xiong Y, Wang Y, Meng Y, Zhang W, Shen M, Zhang X, Li S, Ren B, Li R, Han Y, Zhang J, Cao S, Du W, Sun Q, Wei F, An X, Yang L, Zhang Y, Ma W, Xu W, Zhang Y, Jiang J, Xu X, Xia J, Liu L, Ren X. A Phase IB Trial of Autologous Cytokine-Induced Killer Cells in Combination with Sintilimab, Monoclonal Antibody Against Programmed Cell Death-1, plus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2022 Dec;23(8):709-719. doi: 10.1016/j.cllc.2022.07.009. Epub 2022 Jul 21.

Reference Type: DERIVED

PMID: 35995696 (View on PubMed)

Other Identifiers

E2019091A

Identifier Type: -

Identifier Source: org_study_id