Personalized Reduction of Chemotherapy Intensity Through ctDNA Evaluation for the Treatment of Patients With Advanced Hodgkin Lymphoma

NCT06745076 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: RG1124935NCI-2024-0981520689
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 5

Brief Summary

This phase II trial tests how well personalized reduction of chemotherapy (nivolumab, doxorubicin, vinblastine and dacarbazine) based on circulating tumor deoxyribonucleic acid (ctDNA) evaluation works for treating patients with Hodgkin lymphoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Chemotherapy drugs, such as nivolumab, doxorubicin, vinblastine and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Many types of tumors tend to lose cells or release different types of cellular products including their DNA, which is referred to as ctDNA, into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids and, based on the result, assign patients to a reduced number of chemotherapy treatments or the standard number of chemotherapy treatments. Using ctDNA to assign a personalized reduction of chemotherapy may be effective in treating patients with advanced Hodgkin lymphoma.

Conditions

Advanced Hodgkin Lymphoma; Classic Hodgkin Lymphoma; Lugano Classification Stage III Hodgkin Lymphoma AJCC v8; Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) in patients with undetectable minimal residual disease (MRD) after 2 cycles of treatment

  At 1 year

Secondary Outcomes (3)

• PFS in MRD positive patients after 2 cycles of treatment

  At 1 year

• PFS in the overall cohort

  At 2 years

• Best response

  Up to 5 years

Study Arms (2)

Arm I (MRD negative)

EXPERIMENTAL

CYCLES 1-2: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo MRD testing. CYCLES 3-4: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression of unacceptable toxicity. CYCLES 5-6: Patients receive nivolumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan, PET/CT scan, questionnaire and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dacarbazine; Drug: Doxorubicin; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Biological: Nivolumab; Procedure: Positron Emission Tomography; Drug: Vinblastine; Other: Questionnaire

Arm II (MRD positive)

EXPERIMENTAL

CYCLES 1-2: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo MRD testing. CYCLES 3-6: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 4 additional cycles (total of 6 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan, PET/CT scan, questionnaire and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dacarbazine; Drug: Doxorubicin; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Biological: Nivolumab; Procedure: Positron Emission Tomography; Drug: Vinblastine; Other: Questionnaire

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (MRD negative); Arm II (MRD positive)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Arm I (MRD negative); Arm II (MRD positive)

Dacarbazine DRUG

Given IV

Also known as: 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007

Arm I (MRD negative); Arm II (MRD positive)

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Arm I (MRD negative); Arm II (MRD positive)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Arm I (MRD negative); Arm II (MRD positive)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Arm I (MRD negative); Arm II (MRD positive)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Arm I (MRD negative); Arm II (MRD positive)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm I (MRD negative); Arm II (MRD positive)

Vinblastine DRUG

Given IV

Also known as: Vincaleucoblastine, VLB

Arm I (MRD negative); Arm II (MRD positive)

Questionnaire OTHER

Complete questionnaire

Arm I (MRD negative); Arm II (MRD positive)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Classical Hodgkin lymphoma without prior systemic therapy, stage 3 or 4. Corticosteroids for symptom relief are allowed
• Measurable disease per Lugano criteria
• Patients must be appropriate candidates for 6 cycles of combination chemotherapy including an anthracycline
• No evidence of active central nervous system lymphoma
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) ≥ 500/mm\^3. Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. There is no lower limit to cytopenias if related to bone marrow involvement or underlying Hodgkin lymphoma
• Platelets ≥ 50,000/mm\^3 (without transfusion or growth factor support). Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. There is no lower limit to cytopenias if related to bone marrow involvement or underlying Hodgkin lymphoma
• Hemoglobin ≥ 8 g/dL. Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. There is no lower limit to cytopenias if related to bone marrow involvement or underlying Hodgkin lymphoma
• Serum creatinine \< 1.5 x upper limits of normal (ULN) or creatinine clearance greater than 30/ml per minute by Cockcroft Gault formula
• Total bilirubin ≤ 1.5 times upper limit of normal OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN). Patients with Gilbert Syndrome and direct bilirubin \< 1.5 x ULN or confirmatory UGT1A1 testing are allowed to enroll
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal (≤ 5 × ULN for participants with liver involvement)
• Patients must be age 18 or older
• All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
• Patients must be anticipated to complete all planned study therapy
• Male patients must agree to use an adequate method of barrier contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

You may not qualify if:

• Patients known positive for HIV or infectious hepatitis type B or C with a detectable viral load may not participate. Hepatitis B/C, and HIV testing are not required at screening unless mandated by local health authority.
• Patients living with HIV, on anti-viral treatment and undetectable viral load are allowed
• Patients with positive hepatitis (hep) B core antibody are allowed on study with an undetectable viral load and appropriate prophylaxis
• Patients with positive hepatitis C antibody are allowed with undetectable viral load
• Pregnant or nursing women. Men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 2 years or greater, unless approved by the principal investigator
• Patients who have other medical conditions that would contraindicate treatment with aggressive chemotherapy (including active infection, uncontrolled hypertension, congestive heart failure, unstable angina pectoris, or myocardial infarction within the past 6 months, uncontrolled arrhythmia, severe pulmonary disease or requirement of supplemental oxygen)
• Active ischemic heart disease (eg. myocardial infarction within 6 months) or congestive heart failure (eg. left ventricular ejection fraction \< 50%)
• Concurrent use of other anti-cancer agents or experimental treatments
• Known current or prior autoimmune disease with the exception of vitiligo. Patients with a history of autoimmune thyroid disease on a stable dose of thyroid hormone are also allowed
• Active or prior history of pneumonitis/interstitial lung disease that required corticosteroids
• Current use of supplemental oxygen
• Is known to have received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of trial treatment. Other non-live or live-attenuated vaccines (eg. COVID, Influenza) are allowed

Sponsors & Collaborators

• University of Washington: lead

Study Sites (5)

City of Hope

Irvine, California, 92618, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Washington University in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Dacarbazine; Doxorubicin; Nivolumab; Magnetic Resonance Spectroscopy; Vinblastine; Surveys and Questionnaires

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Ryan Lynch, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hongyan Du, Ph.D.

CONTACT

206.606.1221; hongydu@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: December 20, 2024
• Study Start: March 6, 2025
• Primary Completion (Estimated): January 3, 2032
• Study Completion (Estimated): January 3, 2033
• Last Updated: March 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)