A Single-Center Pilot Study Evaluating the Efficacy and Safety of First-Line Immunochemotherapy With Nivolumab Guided by Interim PET for Stratification and Hazard Minimization in Patients With Advanced Classical Hodgkin Lymphoma (FINISH-HL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Proportion of patients achieving complete metabolic response (CMR) after 2 cycles of induction therapy
研究概览
简要总结
This is a single-center, open-label, phase 2 pilot study evaluating the efficacy and safety of a response-adapted first-line treatment strategy for patients with classical Hodgkin lymphoma (cHL) and unfavorable prognostic factors. The FINISH protocol (First-line Immuno-chemotherapy Navigated by Interim PET for Stratification and Hazard minimization In Hodgkin lymphoma) integrates nivolumab into induction therapy and tailors subsequent treatment based on interim PET-CT response. The study also includes exploratory monitoring of circulating tumor DNA (ctDNA) to investigate its role in early response assessment and residual disease detection.
详细描述
The FINISH study (First-line Immuno-chemotherapy Navigated by Interim PET for Stratification and Hazard minimization In Hodgkin lymphoma) is designed to evaluate a novel personalized treatment strategy for newly diagnosed patients with classical Hodgkin lymphoma (cHL) and advanced-stage or bulky disease. All participants receive initial immunochemotherapy with nivolumab plus EACOPD-14. Treatment is then adapted based on interim PET-CT after two cycles. Patients with a complete metabolic response (Deauville score 1-3) receive de-escalated consolidation with Nivo-AVD followed by nivolumab monotherapy. Patients with inadequate metabolic response undergo continued or intensified therapy based on further PET response.
In addition to clinical and imaging-based endpoints, the study incorporates exploratory monitoring of circulating tumor DNA (ctDNA) at predefined time points. This includes analysis of ctDNA kinetics and correlation with PET response, aiming to develop a molecular framework for response stratification and early detection of residual disease.
The primary goal is to increase treatment efficacy while minimizing long-term toxicity through PET-guided de-escalation and early immunotherapy integration. Safety, feasibility, and molecular response patterns will be analyzed to inform future trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent prior to any study-specific procedures
- •Histologically confirmed classical Hodgkin lymphoma (cHL)
- •Newly diagnosed disease, Ann Arbor stage IIB (bulky), III, or IV
- •At least one measurable lesion ≥15 mm in the longest diameter (by CT)
- •Age between 18 and 60 years (inclusive)
- •ECOG performance status 0-2
- •PET-CT performed at baseline
- •No prior chemotherapy, radiotherapy, or immunotherapy for lymphoma
- •Adequate organ function, including:
- •Serum creatinine ≤ 0.2 mmol/L
- •Absence of severe cardiac, pulmonary, hepatic, or renal dysfunction
- •Ability to comply with the study protocol and scheduled visits
排除标准
- •Active hepatitis B or C infection
- •Positive test for HIV
- •Pregnancy or breastfeeding
- •Prior or active autoimmune disease requiring systemic therapy
- •Vaccination with a live vaccine within 30 days prior to first nivolumab dose
- •History of non-infectious pneumonitis requiring corticosteroids
- •Prior malignancy (except for adequately treated basal cell carcinoma or cervical carcinoma in situ)
- •Congestive heart failure, unstable angina, recent myocardial infarction, or severe cardiac arrhythmias
- •Severe renal impairment (serum creatinine > 0.2 mmol/L), unless lymphoma-related
- •Severe hepatic dysfunction, unless directly related to lymphoma
- •Severe pneumonia with respiratory failure or hypoxemia not corrected within 2-3 days
- •Sepsis or hemodynamic instability
- •Life-threatening bleeding events (e.g., gastrointestinal or cerebral hemorrhage)
- •Cachexia (total serum protein < 35 g/L), unless due to lymphoma-related liver damage
- •Decompensated diabetes mellitus
- •Any somatic or psychiatric condition that, in the investigator's judgment, precludes informed consent or study participation
研究组 & 干预措施
Response-adapted immunochemotherapy (FINISH protocol)
All participants receive induction immunochemotherapy with nivolumab and EACOPD-14 (2 cycles). Based on interim PET-CT after 2 cycles:
- PET-negative (Deauville 1-3): de-escalated consolidation with Nivolumab + AVD ×2, followed by nivolumab monotherapy ×2
- PET-positive (Deauville ≥4): continuation of Nivo-EACOPD-14 ×2 (total 4 cycles).
2.1. If PET becomes negative after 4 cycles: consolidation with Nivo-EACOPD-14 ×2 2.2. If PET remains positive after 4 cycles: patient is withdrawn from the protocol
Circulating tumor DNA (ctDNA) is collected at baseline, after 2, 4, and 6 cycles for exploratory molecular response assessment.
干预措施: Nivolumab (Drug)
Response-adapted immunochemotherapy (FINISH protocol)
All participants receive induction immunochemotherapy with nivolumab and EACOPD-14 (2 cycles). Based on interim PET-CT after 2 cycles:
- PET-negative (Deauville 1-3): de-escalated consolidation with Nivolumab + AVD ×2, followed by nivolumab monotherapy ×2
- PET-positive (Deauville ≥4): continuation of Nivo-EACOPD-14 ×2 (total 4 cycles).
2.1. If PET becomes negative after 4 cycles: consolidation with Nivo-EACOPD-14 ×2 2.2. If PET remains positive after 4 cycles: patient is withdrawn from the protocol
Circulating tumor DNA (ctDNA) is collected at baseline, after 2, 4, and 6 cycles for exploratory molecular response assessment.
干预措施: N-EACOPD-14 (Other)
Response-adapted immunochemotherapy (FINISH protocol)
All participants receive induction immunochemotherapy with nivolumab and EACOPD-14 (2 cycles). Based on interim PET-CT after 2 cycles:
- PET-negative (Deauville 1-3): de-escalated consolidation with Nivolumab + AVD ×2, followed by nivolumab monotherapy ×2
- PET-positive (Deauville ≥4): continuation of Nivo-EACOPD-14 ×2 (total 4 cycles).
2.1. If PET becomes negative after 4 cycles: consolidation with Nivo-EACOPD-14 ×2 2.2. If PET remains positive after 4 cycles: patient is withdrawn from the protocol
Circulating tumor DNA (ctDNA) is collected at baseline, after 2, 4, and 6 cycles for exploratory molecular response assessment.
干预措施: N-AVD (Other)
结局指标
主要结局
Proportion of patients achieving complete metabolic response (CMR) after 2 cycles of induction therapy
时间窗: 4 weeks after treatment initiation
Complete metabolic response is defined as Deauville score 1-3 on PET-CT after two cycles of Nivolumab + EACOPD-14, assessed per LYRIC criteria.
Time to CMR
时间窗: Up to 6 cycles (approximately 12-14 weeks)
Time from first dose of study treatment to the first documentation of complete metabolic response (Deauville 1-3) by PET-CT. If CMR is not achieved, patients are censored at last PET assessment.
Proportion of patients achieving CMR at PET-2, PET-4, and PET-6
时间窗: Up to 18 weeks after first dose
Rate of complete metabolic response (Deauville 1-3) assessed at interim and end-of-treatment PET-CT scans after 2, 4, and 6 cycles of therapy.
次要结局
- Overall Survival (OS)(Up to 24 months)
- Progression-Free Survival (PFS)(Up to 24 months)
- Event-Free Survival (EFS)(Up to 24 months)
- Duration of metabolic response(Up to 24 months)
- Overall Response Rate (ORR) at PET-2, PET-4, and PET-6(PET-2 (Week 4), PET-4 (Week 8), PET-6 (Week 12-14))
- Incidence and severity of treatment-emergent adverse events(From first dose until 90 days after last treatment)