PET-Adapted First-Line Therapy With Nivolumab for Advanced Hodgkin Lymphoma

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Nivolumab
  Monoclonal antibody targeting PD-1; administered in combination regimens
• Другое N-EACOPD-14
  14-day regimen. Combination of Nivolumab with Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, and Dacarbazine; given for 2 cycles as initial therapy.
• Другое N-AVD
  Combination of Nivolumab with Doxorubicin, Vinblastine, and Dacarbazine; used as de-escalated therapy after negative interim PET (2 cycles).

Первичные конечные точки

• Proportion of patients achieving complete metabolic response (CMR) after 2 cycles of induction therapy [Срок оценки: 4 weeks after treatment initiation]
• Time to CMR [Срок оценки: Up to 6 cycles (approximately 12-14 weeks)]
• Proportion of patients achieving CMR at PET-2, PET-4, and PET-6 [Срок оценки: Up to 18 weeks after first dose]

Вторичные конечные точки (6)

• Overall Survival (OS) [Срок оценки: Up to 24 months]
• Progression-Free Survival (PFS) [Срок оценки: Up to 24 months]
• Event-Free Survival (EFS) [Срок оценки: Up to 24 months]
• Duration of metabolic response [Срок оценки: Up to 24 months]
• Overall Response Rate (ORR) at PET-2, PET-4, and PET-6 [Срок оценки: PET-2 (Week 4), PET-4 (Week 8), PET-6 (Week 12-14)]
• Incidence and severity of treatment-emergent adverse events [Срок оценки: From first dose until 90 days after last treatment]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Россия · 1 центр

• National Medical Research Center for Hematology — Moscow

Идентификаторы

NCT: NCT07209059 · HL-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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