Advanced Hodgkin Lymphoma, Hodgkin Disease, Hodgkin Lymphoma
Conditions
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
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.
Interventions
DRUGNivolumab
Monoclonal antibody targeting PD-1; administered in combination regimens
OTHERN-EACOPD-14
14-day regimen. Combination of Nivolumab with Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, and Dacarbazine; given for 2 cycles as initial therapy.
OTHERN-AVD
Combination of Nivolumab with Doxorubicin, Vinblastine, and Dacarbazine; used as de-escalated therapy after negative interim PET (2 cycles).
Sponsors
National Research Center for Hematology, Russia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation between ctDNA clearance and PET-defined metabolic response | Up to 14 weeks | Correlation coefficient between ctDNA clearance (yes/no, as determined by NGS assay) and PET response (Deauville 1-3 vs ≥4) at PET-2, PET-4, and PET-6. |
| Change in circulating tumor DNA (ctDNA) concentration during treatment | From Day 0 to end of treatment (approximately 12-14 weeks) | Quantitative change in ctDNA levels at baseline, after 2 cycles (PET-2), after 4 cycles (PET-4), and at the end of therapy. |
| ctDNA-based molecular profile of patients resistant to PD-1 blockade | At baseline and at progression (up to 2 years) | Detection of specific mutations and clonal dynamics in patients with insufficient response to nivolumab-based therapy. |
| Prognostic value of detectable ctDNA at the end of therapy | Up to 24 months | Kaplan-Meier estimated PFS in patients stratified by ctDNA status (positive vs negative) at end of treatment. |
Countries
Russia
Contacts
Primary ContactAnna A Kravtsova, MD
Backup ContactYana K Mangasarova, MD
Outcome results
None listed