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

Official title

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)

Overview

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (6)

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

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Russia · 1 center

• National Medical Research Center for Hematology — Moscow

Identifiers

NCT: NCT07209059 · HL-2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗