PET-Adapted First-Line Therapy With Nivolumab for Advanced Hodgkin Lymphoma (FINISH-HL)

National Research Center for Hematology, Russia

Status and phase: Enrolling; Phase 2

Conditions: Hodgkin Lymphoma; Hodgkin Disease; Advanced Hodgkin Lymphoma

Treatments: Other: N-EACOPD-14; Drug: Nivolumab; Other: N-AVD

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT07209059

HL-2025

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Response-adapted immunochemotherapy (FINISH protocol)

Experimental group

Description:

All participants receive induction immunochemotherapy with nivolumab and EACOPD-14 (2 cycles). Based on interim PET-CT after 2 cycles: 1. PET-negative (Deauville 1-3): de-escalated consolidation with Nivolumab + AVD ×2, followed by nivolumab monotherapy ×2 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.

Treatment:

Other: N-AVD

Drug: Nivolumab

Other: N-EACOPD-14