PET-Adapted First-Line Therapy With Nivolumab for Advanced Hodgkin Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-60
SponsorNational Research Center for Hematology, Russia
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
Active hepatitis B or C infection
Positive test for HIV
Pregnancy or breastfeeding
Prior or active autoimmune disease requiring systemic therapy
Trial design
Design model
Single group
Treatments tested in this trial
Nivolumab
DrugMonoclonal antibody targeting PD-1; administered in combination regimens
N-EACOPD-14
Other intervention14-day regimen. Combination of Nivolumab with Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, and Dacarbazine; given for 2 cycles as initial therapy.
N-AVD
Other interventionCombination of Nivolumab with Doxorubicin, Vinblastine, and Dacarbazine; used as de-escalated therapy after negative interim PET (2 cycles).
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Response-adapted immunochemotherapy (FINISH protocol)Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
4 weeks after treatment initiation2
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.
Time frame
Up to 6 cycles (approximately 12-14 weeks)3
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.
Time frame
Up to 18 weeks after first doseSecondary outcomes
1
Overall Survival (OS)
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.
Time frame
Up to 24 months2
Progression-Free Survival (PFS)
Time from first dose of treatment to documented disease progression or death, whichever occurs first. Progression is defined according to LYRIC criteria.
Time frame
Up to 24 months3
Event-Free Survival (EFS)
Time from start of therapy to first documented disease progression, relapse, treatment discontinuation for any reason, or death.
Time frame
Up to 24 months4
Duration of metabolic response
Time from first PET-defined complete metabolic response (Deauville 1-3) to documented disease progression or relapse.
Time frame
Up to 24 monthsOther outcomes
1
Change in circulating tumor DNA (ctDNA) concentration during treatment
Quantitative change in ctDNA levels at baseline, after 2 cycles (PET-2), after 4 cycles (PET-4), and at the end of therapy.
Time frame
From Day 0 to end of treatment (approximately 12-14 weeks)2
Correlation between ctDNA clearance and PET-defined metabolic response
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.
Time frame
Up to 14 weeks3
Prognostic value of detectable ctDNA at the end of therapy
Kaplan-Meier estimated PFS in patients stratified by ctDNA status (positive vs negative) at end of treatment.
Time frame
Up to 24 months4
ctDNA-based molecular profile of patients resistant to PD-1 blockade
Detection of specific mutations and clonal dynamics in patients with insufficient response to nivolumab-based therapy.
Time frame
At baseline and at progression (up to 2 years)Sponsors and contacts
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Source ClinicalTrials.gov