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

NCT ID: NCT07209059

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-29
• Study Completion Date: 2028-12-31

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.

Conditions

Hodgkin Lymphoma; Hodgkin Disease; Advanced Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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:

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Monoclonal antibody targeting PD-1; administered in combination regimens

N-EACOPD-14

Intervention Type: OTHER

14-day regimen. Combination of Nivolumab with Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, and Dacarbazine; given for 2 cycles as initial therapy.

N-AVD

Intervention Type: OTHER

Combination of Nivolumab with Doxorubicin, Vinblastine, and Dacarbazine; used as de-escalated therapy after negative interim PET (2 cycles).

Interventions

Nivolumab

Monoclonal antibody targeting PD-1; administered in combination regimens

Intervention Type: DRUG

N-EACOPD-14

14-day regimen. Combination of Nivolumab with Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, and Dacarbazine; given for 2 cycles as initial therapy.

Intervention Type: OTHER

N-AVD

Combination of Nivolumab with Doxorubicin, Vinblastine, and Dacarbazine; used as de-escalated therapy after negative interim PET (2 cycles).

Intervention Type: OTHER

Other Intervention Names

Opdivo; Nivolumab + EACOPD; Nivolumab + AVD

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Research Center for Hematology, Russia

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evgeny E Zvonkov, MD, PhD

Role: STUDY_DIRECTOR

National Medical Research Center for Hematology

Locations

National Medical Research Center for Hematology

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Anna A Kravtsova, MD

Role: CONTACT

kravtsovaanna95@gmail.com

+74956122361

Yana K Mangasarova, MD

Role: CONTACT

v.k.jana@mail.ru

+74956122361

Facility Contacts

Anna A Kravtsova, MD

Role: primary

kravtsovaanna95@gmail.com

Other Identifiers

HL-2025

Identifier Type: -

Identifier Source: org_study_id