A Randomized Controlled Multicenter Phase 2 Clinical Trial of Golidocitinib Combined With P-GemOx Plus PD-1 Inhibitor Versus P-GemOx Plus PD-1 Inhibitor in the Treatment of First-Line Newly Diagnosed Advanced Extranodal NK/T-Cell Lymphoma (ENKTL) or Non-Nasal Extranodal NK/T-Cell Lymphoma (ENKTL)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 主要终点
- Complete Response Rate (CRR) After 6 Cycles of Induction Therapy
研究概览
简要总结
This is a multicenter, randomized, Phase 2 clinical trial designed to evaluate the efficacy and safety of golidocitinib combined with the P-GemOx (pegaspargase + gemcitabine + oxaliplatin) regimen plus PD-1 inhibitor, compared with P-GemOx plus PD-1 inhibitor alone, in participants with first-line newly diagnosed advanced (Stage III-IV) or non-nasal extranodal natural killer/T-cell lymphoma (ENKTL). Eligible participants will be randomly assigned 1:1 to two groups:
Experimental group: Golidocitinib (150 mg orally once daily, Days 1-21 per 21-day cycle) + P-GemOx (pegaspargase 2000 U/m² on Day 2; gemcitabine 1000 mg/m² on Day 1; oxaliplatin 100 mg/m² on Day 1, per 21-day cycle) + PD-1 inhibitor (200 mg intravenously on Day 1 per 21-day cycle).
Control group: P-GemOx + PD-1 inhibitor (same dosage/schedule as the experimental group, without golidocitinib). All participants will receive 6 cycles of induction therapy. Those achieving CR or partial response (PR) after induction will receive maintenance therapy for 1 year: the experimental group will continue golidocitinib + PD-1 inhibitor, while the control group will receive PD-1 inhibitor alone (both per 21-day cycles). The primary outcome is the complete response rate (CRR) after 6 induction cycles (assessed per the 2014 Lugano Classification for Lymphoma). Secondary outcomes include overall response rate (ORR), 2-year progression-free survival (PFS), 2-year overall survival (OS), and the incidence of treatment-related adverse events (graded per NCI-CTCAE Version 5.0). 40 participants will be enrolled across multiple Chinese medical centers. This Phase 2 trial will provide preliminary evidence to determine whether the golidocitinib combination regimen is a safe and effective first-line option for advanced or non-nasal ENKTL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily provides written informed consent (ICF) prior to any study procedures.
- •Aged 18-70 years (inclusive), regardless of sex.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Histologically confirmed extranodal NK/T-cell lymphoma (ENKTL), staged as Stage III-IV or non-nasal ENKTL (per 2016 WHO Classification of Hematopoietic and Lymphoid Tumors).
- •At least one measurable/evaluable lesion (per 2014 Lugano Classification: measurable lesion ≥1.5 cm in longest diameter + ≥1.0 cm in shortest diameter; evaluable lesion with FDG uptake higher than liver on PET/CT).
- •Treatment-naive (no prior anti-cancer therapy for ENKTL).
- •Adequate organ function:
- •AST/ALT ≤2.5×upper limit of normal (ULN); Total bilirubin (TBIL) ≤1.5×ULN; Serum creatinine <1.5×ULN or creatinine clearance (CrCl, via Cockcroft-Gault formula) ≥60 mL/min.
- •Reproductive-aged females have a negative pregnancy test at screening; all participants use effective contraception during the study and for 12 months after the last dose.
- •Expected survival ≥6 months.
排除标准
- •Complicated by hemophagocytic lymphohistiocytosis (HLH) or aggressive NK-cell leukemia.
- •Contraindication to golidocitinib, PD-1 inhibitor, or any component of the P-GEMOX regimen.
- •Lymphoma involvement of the central nervous system (CNS).
- •Major surgery (excluding diagnostic biopsy) within 4 weeks prior to study treatment initiation.
- •History of other malignant tumors (except curatively treated in situ cancers, e.g., cervical carcinoma in situ) within 5 years.
- •Uncontrolled severe comorbidities (e.g., NYHA Class II+ heart failure, unstable angina, myocardial infarction within 1 year, uncontrolled arrhythmias).
- •Active bleeding (e.g., gastrointestinal hemorrhage, cerebral hemorrhage).
- •Uncontrolled infection (requiring parenteral anti-infective therapy) within 7 days prior to study treatment.
- •Active hepatitis B/C: HBsAg+/HBcAb+ with HBV-DNA >2500 copies/mL (or 500 IU/mL); HCV antibody+ with positive HCV-RNA.
- •HIV infection or acquired immunodeficiency syndrome (AIDS).
- •Conditions impairing drug absorption (e.g., inability to swallow tablets, malabsorption syndrome).
- •Pregnant/lactating females, or reproductive-aged participants refusing contraception.
- •Psychiatric illness precluding informed consent or study compliance.
- •Other conditions deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
Golidocitinib + P-GemOx + PD-1 Inhibitor
Golidocitinib (150 mg orally once daily, Days 1-21) Pegaspargase (2000 U/m² intravenously, Day 2) Gemcitabine (1000 mg/m² intravenously, Day 1) Oxaliplatin (100 mg/m² intravenously, Day 1) PD-1 inhibitor (200 mg intravenously, Day 1) Participants receive 6 cycles of induction therapy; those achieving complete response (CR) or partial response (PR) will continue maintenance therapy (Golidocitinib + PD-1 inhibitor, same dosage/schedule) for 1 year or until disease progression.
干预措施: Golidocitinib in combination with P-GEMOX and PD-1 inhibitor (Drug)
P-GemOx + PD-1 Inhibitor
Pegaspargase (2000 U/m² intravenously, Day 2) Gemcitabine (1000 mg/m² intravenously, Day 1) Oxaliplatin (100 mg/m² intravenously, Day 1) PD-1 inhibitor (200 mg intravenously, Day 1) Participants receive 6 cycles of induction therapy; those achieving complete response (CR) or partial response (PR) will continue maintenance therapy (PD-1 inhibitor alone, same dosage/schedule) for 1 year or until disease progression.
干预措施: PD-1 inhibitor in combination with P-GEMOX (Drug)
结局指标
主要结局
Complete Response Rate (CRR) After 6 Cycles of Induction Therapy
时间窗: Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 days)
The proportion of evaluable participants who achieve complete response (CR) following 6 cycles of induction therapy. CR is defined in accordance with the 2014 Lugano Classification for Lymphoma: this requires the complete disappearance of all measurable/evaluable lymphoma lesions, resolution of all disease-related clinical symptoms, and normalization of imaging findings (e.g., no residual measurable disease on CT/MRI, and no metabolically active disease on FDG-PET/CT). The analysis population is restricted to participants who complete at least 4 cycles of induction therapy and have available post-treatment efficacy assessment data.
次要结局
- Overall Response Rate (ORR) After 6 Cycles of Induction Therapy(Within 21 days after the completion of the 6th cycle of induction therapy At the end of Cycle 1 (each cycle is 28 days))
- 2-Year Progression-Free Survival (PFS)(Up to 2 years after randomization)
- 2-Year Overall Survival (OS)(Up to 2 years after randomization)
- Incidence of Treatment-Related Adverse Events (TRAE)(From the first dose of study intervention to 30 days after the last dose of study intervention)
研究者
WEI XU
Chief Physician, Department of Hematology
The First Affiliated Hospital with Nanjing Medical University