Skip to content
Triangle logo TriangleGet started
← Study library

NCT03907488 · CITED IN SOURCE DOCUMENTS

Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-08-04

This phase III trial compares immunotherapy drugs (nivolumab or brentuximab vedotin) when given with combination chemotherapy in treating patients with newly diagnosed stage III or IV classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as doxorubicin, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The addition of nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend the time without disease symptoms coming back.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Progression Free Survival (PFS)

→

outcome · POSTED

Overall Survival

→

outcome · POSTED

Event-free Survival (EFS)

→

outcome · POSTED

Number of Participants With of Adverse Events

→

outcome · NOT POSTED

Metabolic Complete Response Rate

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
Inclusion Criteria: * All patients must have histologically confirmed newly diagnosed, previously untreated stage III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified \[NOS\]). Nodular lymphocyte predominant Hodgkin lymphoma is not eligible. * Patients must have bidimensionally measurable disease (at least one lesion with longest diameter \>= 1.5 cm) documented on the Lymphoma Baseline Tumor Assessment Form in Rave. * Patients must have a whole body or limited whole body PET-CT scan performed within 42 days prior to registration. (A contrast-enhanced \[diagnostic\] CT, MRI or MR-PET is acceptable in event that PET-CT is contra-indicated, however if it is later possible to administer a PET-CT, then PET-CT is strongly preferred for the interim scan (after cycle 2) (if performed) and the EOT assessment. Otherwise, if PET-CT is not subsequently possible, then the same modality as baseline must be used throughout the trial.) NOTE: All images from PET-CT, CT, MRI or MR-PET scans performed as standard of care to assess disease (within 42 days prior to registration) must be submitted and associated radiology reports must be submitted. * Patients must be \>= 12 years of age. * Patients must not have received any prior chemotherapy, radiation, or antibody-based treatment for classical Hodgkin lymphoma. Steroid pre-treatment is permitted. * Patients must not have had prior solid organ transplant. * Patients must not have had prior allogeneic stem cell transplantation. * Patients must not have received a live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, Bacillus Calmette-Guerin \[BCG\], oral polio vaccine, and oral typhoid). * At registration, investigator must declare intent-to-treat with residual PET radiation therapy (residual PET RT- RPRT) to be administered after patient completes 6 cycles of therapy if, after end of treatment, the patient meets criteria specified for receiving RT). Patients will be stratified by investigator's intent-to-treat with residual PET RT. * All pediatric patients (\< 18 years of age) will be considered intent-to-treat with Residual PET RT at time of registration. * Patients must have a performance status corresponding to Zubrod scores of 0, 1 or 2. Use Lansky for patients =\< 17 years of age. \*The conversion of the Lansky to Eastern Cooperative Oncology Group (ECOG) scales is intended for National Cancer Institute (NCI) reporting purposes only. * Adults (age 18 or older): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight. Pediatric Patients (age 12-17), the following must have been obtained within 14 days prior to registration: * Measured or calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2, or * Serum creatinine =\< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine (SCr) based on age/gender as follows: * Age \< 13 maximum serum creatinine: Male 1.2 mg/dL; Female 1.2 mg/dL * Age 13 to \< 16 maximum serum creatinine: Male 1.5 mg/dL; Female 1.4 mg/dL * Age 16-17 maximum serum creatinine: Male 1.7 mg/dL; Female 1.4 mg/dL * Total bilirubin =\< 2 x IULN (must be documented within 28 days prior to registration for adults \[age 18 or older\]; must be documented within 14 days prior to registration for pediatric patients \[age 12-17\]). * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x IULN (must be documented within 28 days prior to registration for adults \[age 18 or older\]; must be documented within 14 days prior to registration for pediatric patients \[age 12-17\]). * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Patients must have an echocardiogram (ECHO), multigated acquisition (MUGA), or functional cardiac imaging scan with a left ventricular ejection (LVEF) fraction \>= 50% or a shortening fraction of \>= 27%. For all patients, the ECHO, MUGA, or functional cardiac imaging scan must be performed within 42 days prior to registration. * Patients with known human immunodeficiency virus (HIV) infection must be receiving anti-retroviral therapy and have an undetectable or unquantifiable viral load at their most recent viral load test within 6 months prior to registration. * Patients must not have known active hepatitis B (HBV) or hepatitis C virus (HCV) at date of registration. Patients with previously treated HBV or HCV that have an undetectable viral load within 6 months prior to registration and no residual hepatic impairment are eligible. * Patients must not have any known central nervous system lymphoma. * Patients must not have a history of or active interstitial pneumonitis or interstitial lung disease. * Patients must not have had a diagnosis of inherited or acquired immunodeficiency. * Patients must not have any known uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, hemodynamically unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued prior to cycle 1, day 1. * Patients with peripheral neuropathy must have \< grade 2 at date of registration. * Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10 mg or equivalent). Autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), as well as symptomatic disease (e.g.: rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis or glomerulonephritis). Vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 2 years are permitted. * No second prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, any in situ cancer or other cancer for which the patient has been disease free for two years. * Females of childbearing potential must not be pregnant or nursing, and have a negative pregnancy test within 28 days prior to registration. Women/men of reproductive potential must have agreed to use an effective contraceptive method while receiving study drug and for women until 6 months after receiving the last dose of study drug or, for men, until 7 months after receiving the last dose of study drug. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. * Patients must have one formalin-fixed paraffin embedded (FFPE) diagnostic tumor block or at least 1 diagnostic, 4-5 micron, hematoxylin and eosin (H\&E) slide collected prior to registration and available for submission. * Patients must be offered participation in banking for planned translational medicine and future research. With patient consent, any residuals from the mandatory tissue submission will also be banked for future research. * Patients who can complete Patient-Reported Outcome instruments in English, Spanish, or French must complete the PROMIS Fatigue, the FACT/GOG-Ntx, and the PROMIS Global prior to registration. Patients who do not complete PRO instruments prior to registration but are otherwise eligible will remain eligible for the primary analysis and other secondary analyses. * Patients who can complete Patient-Reported Outcome instruments in English, Spanish, or French must also agree to complete the PROMIS Fatigue, the FACT/GOG-Ntx, the PROMIS Global, and the PRO-CTCAE (or Pediatric \[Ped\] PRO-CTCAE) at the scheduled on-study assessment timepoints. * Patients must be informed of the investigational nature of this study and all patients and/or their parents or legal guardians (for patients \< 18 years of age) must sign and give informed consent and assent (where appropriate) in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board Initiative (CIRB) regulations. * Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
healthy Volunteers
false
minimum Age
12 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, dacarbazine IV, and nivolumab IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim SC on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician. Patients also undergo peripheral blood specimen collection and CT, PET/CT and MRI on study.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Computed Tomography
    3. Drug: Dacarbazine
    4. Drug: Doxorubicin Hydrochloride
    5. Biological: Filgrastim
    6. Procedure: Magnetic Resonance Imaging
    7. Biological: Nivolumab
    8. Biological: Pegfilgrastim
    9. Procedure: Positron Emission Tomography
    10. Other: Quality-of-Life Assessment
    11. Other: Questionnaire Administration
    12. Radiation: Radiation Therapy
    label
    Arm I (chemotherapy, nivolumab, radiation)
    type
    EXPERIMENTAL
  2. description
    Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, dacarbazine IV, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim SC on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician. Patients also undergo peripheral blood specimen collection and CT, PET/CT and MRI on study.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Drug: Brentuximab Vedotin
    3. Procedure: Computed Tomography
    4. Drug: Dacarbazine
    5. Drug: Doxorubicin Hydrochloride
    6. Biological: Filgrastim
    7. Procedure: Magnetic Resonance Imaging
    8. Biological: Pegfilgrastim
    9. Procedure: Positron Emission Tomography
    10. Other: Quality-of-Life Assessment
    11. Other: Questionnaire Administration
    12. Radiation: Radiation Therapy
    label
    Arm II (chemotherapy, brentuximab vedotin, radiation)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Undergo peripheral blood collection
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Sample Collection
    4. Specimen Collection
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Given IV
    name
    Brentuximab Vedotin
    other Names
    1. ADC SGN-35
    2. Adcetris
    3. Anti-CD30 Antibody-Drug Conjugate SGN-35
    4. Anti-CD30 Monoclonal Antibody-MMAE SGN-35
    5. Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
    6. cAC10-vcMMAE
    7. SGN 35
    8. SGN-35
    9. SGN35
    type
    DRUG
  3. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Undergo PET/CT or CT scan
    name
    Computed Tomography
    other Names
    1. CAT
    2. CAT Scan
    3. Computed Axial Tomography
    4. Computerized Axial Tomography
    5. Computerized axial tomography (procedure)
    6. Computerized Tomography
    7. Computerized Tomography (CT) scan
    8. CT
    9. CT Scan
    10. Diagnostic CAT Scan
    11. Diagnostic CAT Scan Service Type
    12. tomography
    type
    PROCEDURE
  4. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Given IV
    name
    Dacarbazine
    other Names
    1. 4-(Dimethyltriazeno)imidazole-5-carboxamide
    2. 5-(Dimethyltriazeno)imidazole-4-carboxamide
    3. Asercit
    4. Biocarbazine
    5. Dacarbazina
    6. Dacarbazina Almirall
    7. Dacarbazine - DTIC
    8. Dacatic
    9. Dakarbazin
    10. Deticene
    11. Detimedac
    12. DIC
    type
    DRUG
  5. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Given IV
    name
    Doxorubicin Hydrochloride
    other Names
    1. 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    2. ADM
    3. Adriacin
    4. Adriamycin
    5. Adriamycin Hydrochloride
    6. Adriamycin PFS
    7. Adriamycin RDF
    8. ADRIAMYCIN, HYDROCHLORIDE
    9. Adriamycine
    10. Adriblastina
    11. Adriblastine
    12. Adrimedac
    type
    DRUG
  6. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Given SC or IV
    name
    Filgrastim
    other Names
    1. Filgrastim Biosimilar Filgrastim-sndz
    2. Filgrastim Biosimilar Tbo-filgrastim
    3. Filgrastim XM02
    4. Filgrastim-aafi
    5. Filgrastim-ayow
    6. Filgrastim-sndz
    7. G-CSF
    8. Granix
    9. Neupogen
    10. Neutroval
    11. Nivestim
    12. Nivestym
    type
    BIOLOGICAL
  7. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Undergo MRI
    name
    Magnetic Resonance Imaging
    other Names
    1. Magnetic Resonance
    2. Magnetic Resonance Imaging (MRI)
    3. Magnetic resonance imaging (procedure)
    4. Magnetic Resonance Imaging Scan
    5. Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
    6. MR
    7. MR Imaging
    8. MRI
    9. MRI Scan
    10. MRIs
    11. NMR Imaging
    12. NMRI
    type
    PROCEDURE
  8. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    description
    Given IV
    name
    Nivolumab
    other Names
    1. ABP 206
    2. BCD-263
    3. BMS 936558
    4. BMS-936558
    5. BMS936558
    6. CMAB819
    7. MDX 1106
    8. MDX-1106
    9. MDX1106
    10. NIVO
    11. Nivolumab Biosimilar ABP 206
    12. Nivolumab Biosimilar BCD-263
    type
    BIOLOGICAL
  9. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Given SC
    name
    Pegfilgrastim
    other Names
    1. Cegfila
    2. Dulastin
    3. Dyrupeg
    4. Filgrastim SD-01
    5. filgrastim-SD/01
    6. Fulphila
    7. Fylnetra
    8. G-Lasta
    9. Grasustek
    10. HSP-130
    11. Jinyouli
    12. Neulasta
    type
    BIOLOGICAL
  10. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Undergo PET/CT scan
    name
    Positron Emission Tomography
    other Names
    1. Medical Imaging, Positron Emission Tomography
    2. PET
    3. PET Scan
    4. Positron emission tomography (procedure)
    5. Positron Emission Tomography Scan
    6. Positron-Emission Tomography
    7. PT
    type
    PROCEDURE
  11. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Ancillary studies
    name
    Quality-of-Life Assessment
    other Names
    1. Quality of Life Assessment
    type
    OTHER
  12. arm Group Labels
    1. Arm I (chemotherapy, nivolumab, radiation)
    2. Arm II (chemotherapy, brentuximab vedotin, radiation)
    description
    Ancillary studies
    name
    Questionnaire Administration
    type
    OTHER
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
994
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Will be reported as the number of participants who have experienced death or progression, measured at two years. Progression will be measured according to the 2014 Lugano classification. Will test the null hypothesis (HR=1) for PFS using stratified log-rank test with a one-sided alpha of 0.021. The analysis will be based on modified intent-to-treat and will include all eligible patients as randomized regardless of treatment received. The one-sided alpha of .021 will control of the overall type-one error of the study (including the 2 interim superiority analyses) to be less than .025.
    measure
    Progression Free Survival (PFS)
    time Frame
    From date of registration to date of first observation of progressive disease, or death due to any cause, assessed at 2 years
secondary Outcomes
  1. description
    Will be reported as the count of participants who have died, measured at two years. Stratified log-rank test at two-sided alpha level of .05.
    measure
    Overall Survival
    time Frame
    From date of registration to two years or death.
  2. description
    Will be reported as count of participants who have experienced an EFS event or death at two years. EFS Events are defined as: * Disease progression/relapse * Administration of non-protocol specified systemic anti-lymphoma therapy (i.e. salvage therapy) at any time after initiation of protocol therapy. * Administration of any non-protocol specified radiation therapy at any time afterinitiation of protocol therapy Will be estimated using Kaplan-Meier method and compared between treatment arms using cox regression model.
    measure
    Event-free Survival (EFS)
    time Frame
    From date of registration to date of first occurrence of EFS event, assessed at 2 years
  3. description
    Only adverse events that are possibly, probably or definitely related to study drug are reported.
    measure
    Number of Participants With of Adverse Events
    time Frame
    Up to 2 years
  4. description
    This outcome measure will be reported by 11/5/2025.
    measure
    Metabolic Complete Response Rate
    time Frame
    4-8 weeks after last dose of study drug
Full study description
brief Summary
This phase III trial compares immunotherapy drugs (nivolumab or brentuximab vedotin) when given with combination chemotherapy in treating patients with newly diagnosed stage III or IV classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as doxorubicin, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The addition of nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend the time without disease symptoms coming back.
detailed Description
PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) in patients with newly diagnosed advanced stage classical Hodgkin lymphoma randomized to N-AVD (nivolumab, doxorubicin hydrochloride \[doxorubicin\], vinblastine sulfate \[vinblastine\], dacarbazine) versus that obtained with BV-AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine). SECONDARY OBJECTIVES: I. To compare overall survival (OS) in patients randomized to N-AVD versus BV-AVD. II. To compare event-free survival (EFS) in patients randomized to N-AVD versus BV-AVD. III. To compare the metabolic complete response (CR) rate at the end of treatment in patients randomized to N-AVD versus BV-AVD. IV. To compare the physician-reported treatment-related adverse event rates between arms stratified by age groups. V. To compare patient-reported symptoms using selected Patient Reported Outcome Common Toxicity Criteria for Adverse Events (PRO-CTCAE) items between arms stratified by age groups. VI. To compare the safety and tolerability of N-AVD versus that of BV-AVD. QUALITY OF LIFE OBJECTIVE: I. To compare between arms patient-reported fatigue, neuropathy and health-related quality of life over time (baseline, beginning of cycle 3, 4-8 weeks after the last dose of protocol therapy \[following last dose of study drug or radiation therapy, whichever is later\], and 1 and 3 years after randomization) using the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue, the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and the PROMIS Global, respectively. BANKING OBJECTIVES: I. To bank specimens for future correlative studies. II. To bank positron emission tomography (PET)-computed tomography (CT) images for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine sulfate IV, dacarbazine IV, and nivolumab IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim subcutaneously (SC) on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician. Patients also undergo peripheral blood specimen collection and CT, PET/CT and/or magnetic resonance imaging (MRI) on study. ARM II: Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, dacarbazine IV, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim SC on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician. Patients also undergo peripheral blood specimen collection and CT, PET/CT and MRI on study. After completion of study treatment and prior to disease progression, patients are followed up every 3 months for the first year, every 6 months for years 2 and 3, then annually until 10 years after registration. Patients are followed up at the time of progression and then annually until 10 years after registration. Patients who receive radiation therapy are followed up at 8-12 weeks after completion of radiation therapy.
Source references
references
  1. citation
    Goyal G, Lurain K, Lopez G, Rutherford SC, Castellino S, Davison K, Evens A, Smith SM, Kelly K, LeBlanc M, Song JY, Odeny T, Ratner L, Friedberg JW, Herrera AF. Nivolumab + Doxorubicin, Vinblastine, and Dacarbazine in HIV-Associated Advanced-Stage Classic Hodgkin Lymphoma. JCO Oncol Adv. 2026 Jan;3(1):e2500143. doi: 10.1200/oa-25-00143. Epub 2026 Feb 26.
    pmid
    42577949
    type
    DERIVED
  2. citation
    Ahmed S, Li H, Herrera AF, Perry AM, Kovach AE, Rutherford SC, Davison K, Castellino SM, Evens AM, Kahl BS, Bartlett N, Leonard JP, Shipp MA, Smith SM, Kelly KM, LeBlanc ML, Friedberg JW, Song JYY. Impact of EBV Status and Histology on Patient Outcomes with Nivolumab-AVD vs BV-AVD in Advanced Classic Hodgkin Lymphoma (S1826). Blood Adv. 2026 Jul 29:bloodadvances.2026021402. doi: 10.1182/bloodadvances.2026021402. Online ahead of print.
    pmid
    42526889
    type
    DERIVED
  3. citation
    Castellino SM, Li H, Herrera AF, LeBlanc M, Parsons SK, Unger JM, Punnett A, Hodgson D, Keller FG, Drachtman RA, Lamble A, Forlenza CJ, Doan A, Rutherford SC, Evens AM, Little RF, Smith MA, Hoppe BS, Song JY, Smith SM, Friedberg JW, Kelly KM. Three-Year Follow-Up of Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Adolescents With Advanced-Stage Classic Hodgkin Lymphoma on S1826. J Clin Oncol. 2026 Feb 20;44(6):449-454. doi: 10.1200/JCO-25-00203. Epub 2026 Jan 9.
    pmid
    41512237
    type
    DERIVED
  4. citation
    Herrera AF, LeBlanc M, Castellino SM, Li H, Rutherford SC, Evens AM, Davison K, Punnett A, Parsons SK, Ahmed S, Casulo C, Bartlett NL, Tuscano JM, Mei MG, Hess BT, Jacobs R, Saeed H, Torka P, Hu B, Moskowitz C, Kaur S, Goyal G, Forlenza C, Doan A, Lamble A, Kumar P, Chowdhury S, Brinker B, Sharma N, Singh A, Blum KA, Perry AM, Kovach AE, Hodgson D, Constine LS, Shields LK, Prica A, Dillon H, Little RF, Shipp MA, Crump M, Kahl B, Leonard JP, Smith SM, Song JY, Kelly KM, Friedberg JW. Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma. N Engl J Med. 2024 Oct 17;391(15):1379-1389. doi: 10.1056/NEJMoa2405888.
    pmid
    39413375
    type
    DERIVED
  5. citation
    McKenna M, Ryu Tiger YK, Rutherford SC, Evens AM. The Management of older patients with Hodgkin lymphoma: implications of S1826. Semin Hematol. 2024 Aug;61(4):236-244. doi: 10.1053/j.seminhematol.2024.05.004. Epub 2024 Jun 4.
    pmid
    38945791
    type
    DERIVED
  6. citation
    Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.
    pmid
    37505794
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-092f3caf695452e5befa
      requested nct id
      NCT03907488
      primary nct id
      NCT03907488
      source kind
      fda_approval_notice
      source record id
      fda-491ef4b41b9bb54f
      source file sha256
      9ac6a6b28118a1702811db77510dac5e9fd62b8c44f56c18075dc019120a4da0
      payload sha256
      5cbe8f0adeb1178549b8f558df6731680ca8a2f60a35905f030f8e812da344a5
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-092f3caf695452e5befa
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT03907488
      occurrences
      1. context exact
        af/index.cfm">Drugs@FDA</a>.&nbsp;</p><h2>Efficacy and Safety</h2><p>Efficacy of nivolumab in combination with AVD was evaluated in Study CA209-8UT (SWOG 1826; NCT03907488), a randomized, open-label, multicenter trial in patients 12 years and older with previously untreated, Stage III and IV cHL. A total of 994 patients were rand
        end
        25174
        exact text
        NCT03907488
        start
        25163
      offset unit
      unicode_code_points
      source event date
      2026-03-20
      source file
      /tmp/cancer-full-research/updates/pages/fda-approves-nivolumab-chemotherapy-previously-untreated-hodgkin-lymphoma.html
      source file sha256
      9ac6a6b28118a1702811db77510dac5e9fd62b8c44f56c18075dc019120a4da0
      source json pointer
      Source null
      source kind
      fda_approval_notice
      source record id
      fda-491ef4b41b9bb54f
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      9ac6a6b28118a1702811db77510dac5e9fd62b8c44f56c18075dc019120a4da0
      source title
      FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma
    2. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-09e4f5c387b088ac3880
      requested nct id
      NCT03907488
      primary nct id
      NCT03907488
      source kind
      fda_spl_label
      source url
      https://api.fda.gov/drug/label.json?search=%28indications_and_usage%3Acancer+OR+indications_and_usage%3Acarcinoma+OR+indications_and_usage%3Acarcinomas+OR+indications_and_usage%3Alymphoma+OR+indications_and_usage%3Alymphomas+OR+indications_and_usage%3Aleukemia+OR+indications_and_usage%3Aleukaemia+OR+indications_and_usage%3Asarcoma+OR+indications_and_usage%3Asarcomas+OR+indications_and_usage%3Amelanoma+OR+indications_and_usage%3Amyeloma+OR+indications_and_usage%3Atumor+OR+indications_and_usage%3Atumors+OR+indications_and_usage%3Atumour+OR+indications_and_usage%3Atumours+OR+indications_and_usage%3Aneoplasm+OR+indications_and_usage%3Aneoplasms+OR+indications_and_usage%3Amalignant+OR+indications_and_usage%3Amalignancy+OR+indications_and_usage%3Amyelodysplastic+OR+indications_and_usage%3Amyelofibrosis+OR+indications_and_usage%3Amastocytosis+OR+indications_and_usage%3Aglioma+OR+indications_and_usage%3Aglioblastoma+OR+indications_and_usage%3Aneuroblastoma+OR+indications_and_usage%3Aretinoblastoma+OR+indications_and_usage%3Apheochromocytoma+OR+indications_and_usage%3Aparaganglioma+OR+indications_and_usage%3Amyeloproliferative+OR+indications_and_usage%3Awaldenstrom+OR+indications_and_usage%3Apolycythemia+OR+indications_and_usage%3Athrombocythemia+OR+indications_and_usage%3Adesmoid+OR+indications_and_usage%3Aneurofibromatosis+OR+indications_and_usage%3Ahistiocytosis%29+AND+%28openfda.application_number%3ANDA%2A+OR+openfda.application_number%3ABLA%2A%29&limit=100&skip=100&sort=id%3Aasc
      source record id
      1fce9e6a-6a7c-4fc0-a3a4-a0099f7bd2ce
      source file sha256
      fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
      payload sha256
      9c6b95565d5ef28f1a43aaaa7876f37e1f7670a01799aa84418e3ec1d7101442
      payload
      application numbers
      1. BLA125554
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-09e4f5c387b088ac3880
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT03907488
      occurrences
      1. context exact
        al Hodgkin Lymphoma Previously Untreated Classical Hodgkin Lymphoma The efficacy of OPDIVO in combination with AVD was evaluated in Study CA209-8UT (SWOG 1826; NCT03907488), a randomized, open-label, multicenter trial in patients 12 years and older with previously untreated, Stage III and IV cHL. The trial excluded patients with
        end
        57915
        exact text
        NCT03907488
        start
        57904
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/indications/raw/labels-00100.json
      source file sha256
      fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
      source json pointer
      /results/9/clinical_studies/0
      source kind
      fda_spl_label
      source record id
      1fce9e6a-6a7c-4fc0-a3a4-a0099f7bd2ce
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      47f974766bb01dbde354e28e5e29eb6c7328d3adabf94e5593a5044bca4bc462
      source url
      https://api.fda.gov/drug/label.json?search=%28indications_and_usage%3Acancer+OR+indications_and_usage%3Acarcinoma+OR+indications_and_usage%3Acarcinomas+OR+indications_and_usage%3Alymphoma+OR+indications_and_usage%3Alymphomas+OR+indications_and_usage%3Aleukemia+OR+indications_and_usage%3Aleukaemia+OR+indications_and_usage%3Asarcoma+OR+indications_and_usage%3Asarcomas+OR+indications_and_usage%3Amelanoma+OR+indications_and_usage%3Amyeloma+OR+indications_and_usage%3Atumor+OR+indications_and_usage%3Atumors+OR+indications_and_usage%3Atumour+OR+indications_and_usage%3Atumours+OR+indications_and_usage%3Aneoplasm+OR+indications_and_usage%3Aneoplasms+OR+indications_and_usage%3Amalignant+OR+indications_and_usage%3Amalignancy+OR+indications_and_usage%3Amyelodysplastic+OR+indications_and_usage%3Amyelofibrosis+OR+indications_and_usage%3Amastocytosis+OR+indications_and_usage%3Aglioma+OR+indications_and_usage%3Aglioblastoma+OR+indications_and_usage%3Aneuroblastoma+OR+indications_and_usage%3Aretinoblastoma+OR+indications_and_usage%3Apheochromocytoma+OR+indications_and_usage%3Aparaganglioma+OR+indications_and_usage%3Amyeloproliferative+OR+indications_and_usage%3Awaldenstrom+OR+indications_and_usage%3Apolycythemia+OR+indications_and_usage%3Athrombocythemia+OR+indications_and_usage%3Adesmoid+OR+indications_and_usage%3Aneurofibromatosis+OR+indications_and_usage%3Ahistiocytosis%29+AND+%28openfda.application_number%3ANDA%2A+OR+openfda.application_number%3ABLA%2A%29&limit=100&skip=100&sort=id%3Aasc
      spl effective time
      20260812
      spl set id
      f570b9c4-6846-4de2-abfa-4d0a4ae4e394
    3. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-0c27d42dbdfd89bb0e71
      requested nct id
      NCT03907488
      primary nct id
      NCT03907488
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      b73d58cc901225655c1e0b5a529bfad102894e39e86f356aab4e49f88cd28ca1
      payload sha256
      21c4a3251ad047f03bb8ec588a156b4a7f3a815d01ed8add54ced206bffc44cc
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-0c27d42dbdfd89bb0e71
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT03907488
      occurrences
      1. context exact
        ithout nivolumab or brentuximab vedotin):</p> <div class="pdq-content-list"><ol id="_1140"><li>A randomized prospective trial (<a href="/clinicaltrials/NCT03907488">NCT03907488</a>) enrolled 994 patients with previously untreated advanced-stage HL. The study compared BV-AVD with N-AVD.[<a href="#cit/section_7.4">4</a>]<di
        end
        194860
        exact text
        NCT03907488
        start
        194849
      2. context exact
        mab or brentuximab vedotin):</p> <div class="pdq-content-list"><ol id="_1140"><li>A randomized prospective trial (<a href="/clinicaltrials/NCT03907488">NCT03907488</a>) enrolled 994 patients with previously untreated advanced-stage HL. The study compared BV-AVD with N-AVD.[<a href="#cit/section_7.4">4</a>]<div class="pdq-
        end
        194873
        exact text
        NCT03907488
        start
        194862
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/c88b4a702bd9661788.html
      source file sha256
      b73d58cc901225655c1e0b5a529bfad102894e39e86f356aab4e49f88cd28ca1
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:01.623846+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      9a6e61e7bcb841d8aee6690e948cea06b80b68c51413cf7a1eba5ed41d1a2a76
      source title
      Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: February 12, 2025
        datetime
        2025-02-12T12:00:00Z
        display
        February 12, 2025
    4. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-2bd25c105ae89159c9b9
      requested nct id
      NCT03907488
      primary nct id
      NCT03907488
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      bad667e8b37974c2eea779647c1a36ebd0b7bf2bd21d80932a43fbbfa970b044
      payload sha256
      f67245cdd006339970b04444a60d4377bb6ca9f4338a2b60b09ea76b6515a932
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-2bd25c105ae89159c9b9
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT03907488
      occurrences
      1. context exact
        pediatric patients aged 2 years and older with previously untreated high-risk classical Hodgkin lymphoma.</li></ul></div></li><li>The <a href="/clinicaltrials/NCT03907488">S1826 (NCT03907488)</a> phase III study included both adolescents (aged &#8805;12 years) and adults. The study evaluated six cycles of doxorubicin (Adriamycin
        end
        254643
        exact text
        NCT03907488
        start
        254632
      2. context exact
        aged 2 years and older with previously untreated high-risk classical Hodgkin lymphoma.</li></ul></div></li><li>The <a href="/clinicaltrials/NCT03907488">S1826 (NCT03907488)</a> phase III study included both adolescents (aged &#8805;12 years) and adults. The study evaluated six cycles of doxorubicin (Adriamycin), vinblastine, and
        end
        254663
        exact text
        NCT03907488
        start
        254652
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/1f2bb5601361cf87a6.html
      source file sha256
      bad667e8b37974c2eea779647c1a36ebd0b7bf2bd21d80932a43fbbfa970b044
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:01.939351+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      d7e8d8cfdfe7ae2c9a7927a756c5c6fe774ed246c2d070c4f5e8c93f61718cb1
      source title
      Childhood Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 16, 2025
        datetime
        2025-04-16T12:00:00Z
        display
        April 16, 2025

    Preserved source evidence · Not medical advice