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

NCT07209059 | Recruiting Phase 2

• 1 other identifier: HL-2025
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Hodgkin Lymphoma; Hodgkin Disease; Advanced Hodgkin Lymphoma

Keywords

Classical Hodgkin Lymphoma; Hodgkin Disease; Nivolumab; Immunotherapy; First-line treatment; PET-adapted therapy; Checkpoint inhibitors; ctDNA; Response-adapted treatment; EACOPD; AVD; PD-1 blockade; Circulating tumor DNA

Outcome Measures

Primary Outcomes (3)

• Proportion of patients achieving complete metabolic response (CMR) after 2 cycles of induction therapy

  Complete metabolic response is defined as Deauville score 1-3 on PET-CT after two cycles of Nivolumab + EACOPD-14, assessed per LYRIC criteria.

  4 weeks after treatment initiation

• Time to CMR

  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.

  Up to 6 cycles (approximately 12-14 weeks)

• Proportion of patients achieving CMR at PET-2, PET-4, and PET-6

  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.

  Up to 18 weeks after first dose

Secondary Outcomes (6)

• Overall Survival (OS)

  Up to 24 months

• Progression-Free Survival (PFS)

  Up to 24 months

• Event-Free Survival (EFS)

  Up to 24 months

• Duration of metabolic response

  Up to 24 months

• 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)

Other Outcomes (4)

• Change in circulating tumor DNA (ctDNA) concentration during treatment

  From Day 0 to end of treatment (approximately 12-14 weeks)

• Correlation between ctDNA clearance and PET-defined metabolic response

  Up to 14 weeks

• Prognostic value of detectable ctDNA at the end of therapy

  Up to 24 months

Study Arms (1)

Response-adapted immunochemotherapy (FINISH protocol)

EXPERIMENTAL

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.

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

Interventions

Nivolumab DRUG

Monoclonal antibody targeting PD-1; administered in combination regimens

Also known as: Opdivo

Response-adapted immunochemotherapy (FINISH protocol)

N-EACOPD-14 OTHER

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

Also known as: Nivolumab + EACOPD

Response-adapted immunochemotherapy (FINISH protocol)

N-AVD OTHER

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

Also known as: Nivolumab + AVD

Response-adapted immunochemotherapy (FINISH protocol)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Research Center for Hematology, Russia: lead

Study Sites (1)

National Medical Research Center for Hematology

Moscow, 125167, Russia

RECRUITING

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Evgeny E Zvonkov, MD, PhD

  National Medical Research Center for Hematology

  STUDY DIRECTOR

Central Study Contacts

Anna A Kravtsova, MD

CONTACT

+74956122361; kravtsovaanna95@gmail.com

Yana K Mangasarova, MD

CONTACT

+74956122361; v.k.jana@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Single-arm, response-adapted treatment model. All participants receive the same initial induction therapy (Nivolumab + EACOPD-14), followed by PET-guided stratification into de-escalated, continued, or intensified therapy paths. There is no randomization or comparator group.

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: October 6, 2025
• Study Start: July 29, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)