Ignite Creation Date:
2025-12-24 @ 2:23 PM
Ignite Modification Date:
2026-01-01 @ 8:28 AM
Study NCT ID:
NCT07209059
Status:
RECRUITING
Last Update Posted:
2025-10-06
First Post:
2025-07-03
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PET-Adapted First-Line Therapy With Nivolumab for Advanced Hodgkin Lymphoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006689', 'term': 'Hodgkin Disease'}], 'ancestors': [{'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077594', 'term': 'Nivolumab'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-07-29', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2028-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-29', 'studyFirstSubmitDate': '2025-07-03', 'studyFirstSubmitQcDate': '2025-09-29', 'lastUpdatePostDateStruct': {'date': '2025-10-06', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-10-06', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2027-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Change in circulating tumor DNA (ctDNA) concentration during treatment', 'timeFrame': 'From Day 0 to end of treatment (approximately 12-14 weeks)', 'description': 'Quantitative change in ctDNA levels at baseline, after 2 cycles (PET-2), after 4 cycles (PET-4), and at the end of therapy.'}, {'measure': 'Correlation between ctDNA clearance and PET-defined metabolic response', 'timeFrame': 'Up to 14 weeks', 'description': '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.'}, {'measure': 'Prognostic value of detectable ctDNA at the end of therapy', 'timeFrame': 'Up to 24 months', 'description': 'Kaplan-Meier estimated PFS in patients stratified by ctDNA status (positive vs negative) at end of treatment.'}, {'measure': 'ctDNA-based molecular profile of patients resistant to PD-1 blockade', 'timeFrame': 'At baseline and at progression (up to 2 years)', 'description': 'Detection of specific mutations and clonal dynamics in patients with insufficient response to nivolumab-based therapy.'}], 'primaryOutcomes': [{'measure': 'Proportion of patients achieving complete metabolic response (CMR) after 2 cycles of induction therapy', 'timeFrame': '4 weeks after treatment initiation', 'description': 'Complete metabolic response is defined as Deauville score 1-3 on PET-CT after two cycles of Nivolumab + EACOPD-14, assessed per LYRIC criteria.'}, {'measure': 'Time to CMR', 'timeFrame': 'Up to 6 cycles (approximately 12-14 weeks)', 'description': '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.'}, {'measure': 'Proportion of patients achieving CMR at PET-2, PET-4, and PET-6', 'timeFrame': 'Up to 18 weeks after first dose', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Overall Survival (OS)', 'timeFrame': 'Up to 24 months', 'description': '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.'}, {'measure': 'Progression-Free Survival (PFS)', 'timeFrame': 'Up to 24 months', 'description': 'Time from first dose of treatment to documented disease progression or death, whichever occurs first. Progression is defined according to LYRIC criteria.'}, {'measure': 'Event-Free Survival (EFS)', 'timeFrame': 'Up to 24 months', 'description': 'Time from start of therapy to first documented disease progression, relapse, treatment discontinuation for any reason, or death.'}, {'measure': 'Duration of metabolic response', 'timeFrame': 'Up to 24 months', 'description': 'Time from first PET-defined complete metabolic response (Deauville 1-3) to documented disease progression or relapse.'}, {'measure': 'Overall Response Rate (ORR) at PET-2, PET-4, and PET-6', 'timeFrame': 'PET-2 (Week 4), PET-4 (Week 8), PET-6 (Week 12-14)', 'description': 'Proportion of patients with complete or partial metabolic response according to LYRIC and Deauville criteria at each time point.'}, {'measure': 'Incidence and severity of treatment-emergent adverse events', 'timeFrame': 'From first dose until 90 days after last treatment', 'description': 'Number and grade of adverse events according to CTCAE v5.0, including immune-related adverse events, reported throughout treatment.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'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'], 'conditions': ['Hodgkin Lymphoma', 'Hodgkin Disease', 'Advanced Hodgkin Lymphoma']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nIn 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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Signed written informed consent prior to any study-specific procedures\n* Histologically confirmed classical Hodgkin lymphoma (cHL)\n* Newly diagnosed disease, Ann Arbor stage IIB (bulky), III, or IV\n* At least one measurable lesion ≥15 mm in the longest diameter (by CT)\n* Age between 18 and 60 years (inclusive)\n* ECOG performance status 0-2\n* PET-CT performed at baseline\n* No prior chemotherapy, radiotherapy, or immunotherapy for lymphoma\n* Adequate organ function, including:\n* Serum creatinine ≤ 0.2 mmol/L\n* Absence of severe cardiac, pulmonary, hepatic, or renal dysfunction\n* Ability to comply with the study protocol and scheduled visits\n\nExclusion Criteria:\n\n* Active hepatitis B or C infection\n* Positive test for HIV\n* Pregnancy or breastfeeding\n* Prior or active autoimmune disease requiring systemic therapy\n* Vaccination with a live vaccine within 30 days prior to first nivolumab dose\n* History of non-infectious pneumonitis requiring corticosteroids\n* Prior malignancy (except for adequately treated basal cell carcinoma or cervical carcinoma in situ)\n* Congestive heart failure, unstable angina, recent myocardial infarction, or severe cardiac arrhythmias\n* Severe renal impairment (serum creatinine \\> 0.2 mmol/L), unless lymphoma-related\n* Severe hepatic dysfunction, unless directly related to lymphoma\n* Severe pneumonia with respiratory failure or hypoxemia not corrected within 2-3 days\n* Sepsis or hemodynamic instability\n* Life-threatening bleeding events (e.g., gastrointestinal or cerebral hemorrhage)\n* Cachexia (total serum protein \\< 35 g/L), unless due to lymphoma-related liver damage\n* Decompensated diabetes mellitus\n* Any somatic or psychiatric condition that, in the investigator's judgment, precludes informed consent or study participation"}, 'identificationModule': {'nctId': 'NCT07209059', 'acronym': 'FINISH-HL', 'briefTitle': 'PET-Adapted First-Line Therapy With Nivolumab for Advanced Hodgkin Lymphoma', 'organization': {'class': 'NETWORK', 'fullName': 'National Research Center for Hematology, Russia'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': 'HL-2025'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Response-adapted immunochemotherapy (FINISH protocol)', 'description': 'All participants receive induction immunochemotherapy with nivolumab and EACOPD-14 (2 cycles). Based on interim PET-CT after 2 cycles:\n\n1. PET-negative (Deauville 1-3): de-escalated consolidation with Nivolumab + AVD ×2, followed by nivolumab monotherapy ×2\n2. PET-positive (Deauville ≥4): continuation of Nivo-EACOPD-14 ×2 (total 4 cycles).\n\n2.1. 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\n\nCirculating tumor DNA (ctDNA) is collected at baseline, after 2, 4, and 6 cycles for exploratory molecular response assessment.', 'interventionNames': ['Drug: Nivolumab', 'Other: N-EACOPD-14', 'Other: N-AVD']}], 'interventions': [{'name': 'Nivolumab', 'type': 'DRUG', 'otherNames': ['Opdivo'], 'description': 'Monoclonal antibody targeting PD-1; administered in combination regimens', 'armGroupLabels': ['Response-adapted immunochemotherapy (FINISH protocol)']}, {'name': 'N-EACOPD-14', 'type': 'OTHER', 'otherNames': ['Nivolumab + EACOPD'], 'description': '14-day regimen. Combination of Nivolumab with Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, and Dacarbazine; given for 2 cycles as initial therapy.', 'armGroupLabels': ['Response-adapted immunochemotherapy (FINISH protocol)']}, {'name': 'N-AVD', 'type': 'OTHER', 'otherNames': ['Nivolumab + AVD'], 'description': 'Combination of Nivolumab with Doxorubicin, Vinblastine, and Dacarbazine; used as de-escalated therapy after negative interim PET (2 cycles).', 'armGroupLabels': ['Response-adapted immunochemotherapy (FINISH protocol)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '125167', 'city': 'Moscow', 'status': 'RECRUITING', 'country': 'Russia', 'contacts': [{'name': 'Anna A Kravtsova, MD', 'role': 'CONTACT', 'email': 'kravtsovaanna95@gmail.com'}], 'facility': 'National Medical Research Center for Hematology', 'geoPoint': {'lat': 55.75204, 'lon': 37.61781}}], 'centralContacts': [{'name': 'Anna A Kravtsova, MD', 'role': 'CONTACT', 'email': 'kravtsovaanna95@gmail.com', 'phone': '+74956122361'}, {'name': 'Yana K Mangasarova, MD', 'role': 'CONTACT', 'email': 'v.k.jana@mail.ru', 'phone': '+74956122361'}], 'overallOfficials': [{'name': 'Evgeny E Zvonkov, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'National Medical Research Center for Hematology'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Research Center for Hematology, Russia', 'class': 'NETWORK'}, 'responsibleParty': {'type': 'SPONSOR'}}}}