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

A Multicenter Study PRECISE-HL: Personalized Reduction of Chemotherapy Intensity Through ctDNA Evaluation in Advanced Hodgkin Lymphoma

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.

Study Overview

• Status: Recruiting
• Conditions: Classic Hodgkin Lymphoma; Advanced Hodgkin Lymphoma; Lugano Classification Stage III Hodgkin Lymphoma AJCC v8; Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8
• Intervention / Treatment: Biological: Nivolumab; Procedure: Biospecimen Collection; Drug: Dacarbazine; Drug: Doxorubicin; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Multigated Acquisition Scan; Drug: Vinblastine; Other: Questionnaire; Procedure: Echocardiography Test

Detailed Description

OUTLINE:

CYCLES 1-2: Patients receive nivolumab intravenously (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 measurable residual disease (MRD) testing.

Patients who are MRD negative are assigned to Arm I and patients who are MRD positive are assigned to Arm II.

ARM I:

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.

ARM II:

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.

After completion of study treatment, patients are followed up every 3 months for 1 year then periodically for up to 5 years.

Patients undergo echocardiography or MUGA scan, position emission tomography (PET)-computed tomography (CT) scan, questionnaire and blood sample collection throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongyan Du, Ph.D.; Phone Number: 206.606.1221; Email: hongydu@fredhutch.org

Study Locations

• United States
  • California
    • Irvine, California, United States, 92618
      • Not yet recruiting
      • City of Hope
      • Principal Investigator: Azra Borogovac, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: Reid Merryman, MD
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University in St. Louis
      • Principal Investigator: David Russler-Germain, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Alison Moskowitz, MD
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Principal Investigator: Ryan Lynch, MD
      • Contact: Hongyan Du, Ph.D.; Phone Number: 206-606-1221; Email: hongydu@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Female patients of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female patients of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (MRD negative); 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.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo; CMAB819; Nivolumab Biosimilar CMAB819; MDX 1106; MDX1106; BMS 936558; ABP 206; Nivolumab Biosimilar ABP 206; BCD-263; Nivolumab Biosimilar BCD-263; BMS936558; ONO 4538; ONO4538; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Dacarbazine; Given IV; Other Names: 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; Drug: Doxorubicin; Given IV; Other Names: Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Multigated Acquisition Scan; Undergo MUGA scan; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan; RNV Scan; Drug: Vinblastine; Given IV; Other Names: VLB; Vincaleucoblastine; Other: Questionnaire; Complete questionnaire; Procedure: Echocardiography Test; Undergo echocardiography; Other Names: Echocardiography; EC
Experimental: Arm II (MRD positive); 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.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo; CMAB819; Nivolumab Biosimilar CMAB819; MDX 1106; MDX1106; BMS 936558; ABP 206; Nivolumab Biosimilar ABP 206; BCD-263; Nivolumab Biosimilar BCD-263; BMS936558; ONO 4538; ONO4538; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Dacarbazine; Given IV; Other Names: 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; Drug: Doxorubicin; Given IV; Other Names: Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Multigated Acquisition Scan; Undergo MUGA scan; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan; RNV Scan; Drug: Vinblastine; Given IV; Other Names: VLB; Vincaleucoblastine; Other: Questionnaire; Complete questionnaire; Procedure: Echocardiography Test; Undergo echocardiography; Other Names: Echocardiography; EC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival (PFS) in patients with undetectable minimal residual disease (MRD) after 2 cycles of treatment	At 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Ryan Lynch, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2025
• Primary Completion (Estimated): January 3, 2032
• Study Completion (Estimated): January 3, 2033

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Health Care Quality, Access, and Evaluation; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Epidemiologic Methods; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Carbohydrates; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Triazenes; Imidazoles; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Chemistry Techniques, Analytical; Spectrum Analysis; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Nivolumab; Doxorubicin; Dacarbazine; Vinblastine; Surveys and Questionnaires; Specimen Handling; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: RG1124935; NCI-2024-09815 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 20689 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes