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

Not Applicable

Recruiting

• Conditions: Hodgkin Lymphoma; Hodgkin Disease; Advanced Hodgkin Lymphoma
• Interventions: Drug: Nivolumab; Other: N-EACOPD-14; Other: N-AVD

• Registration Number: NCT07209059
• Lead Sponsor: National Research Center for Hematology, Russia

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2025-07-03
• Study Start: 2025-07-29
• Status Verified: 2025-09
• Study First Submitted QC: 2025-09-29
• Last Update Submitted: 2025-09-29
• Study First Posted: 2025-10-06
• Last Update Posted: 2025-10-06
• Primary Completion: 2027-12
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Response-adapted immunochemotherapy (FINISH protocol)	Nivolumab	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.
Response-adapted immunochemotherapy (FINISH protocol)	N-EACOPD-14	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.
Response-adapted immunochemotherapy (FINISH protocol)	N-AVD	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.

Primary Outcome Measures

Name	Time	Method
Proportion of patients achieving complete metabolic response (CMR) after 2 cycles of induction therapy	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	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	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 24 months	Time from the first dose of study treatment to death from any cause. Patients alive at the time of analysis will be censored at the date of last follow-up.
Progression-Free Survival (PFS)	Up to 24 months	Time from first dose of treatment to documented disease progression or death, whichever occurs first. Progression is defined according to LYRIC criteria.
Event-Free Survival (EFS)	Up to 24 months	Time from start of therapy to first documented disease progression, relapse, treatment discontinuation for any reason, or death.
Duration of metabolic response	Up to 24 months	Time from first PET-defined complete metabolic response (Deauville 1-3) to documented disease progression or relapse.
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)	Proportion of patients with complete or partial metabolic response according to LYRIC and Deauville criteria at each time point.
Incidence and severity of treatment-emergent adverse events	From first dose until 90 days after last treatment	Number and grade of adverse events according to CTCAE v5.0, including immune-related adverse events, reported throughout treatment.

Trial Locations

Locations (1)

National Medical Research Center for Hematology; 🇷🇺 Moscow, Russia