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NCT05675410 · CITED IN SOURCE DOCUMENTS

A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab

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
RECRUITING
Registry last update
2026-09-09

This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride 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. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.

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What did the study report?

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

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * Patients must be 5 to 60 years of age at the time of enrollment * Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified \[NOS\]) with stage I or II disease * Patients must have bidimensionally measurable disease (at least one lesion with longest diameter \>= 1.5 cm) * Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained * Pediatric patients (age 5-17 years) with known or suspected mediastinal disease must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease. * Note: Pediatric patients who have received both a CT chest and upright PA CXR may meet the definition of bulk through either modality. * Patients \>= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2 * Patients =\< 17 years of age must have a Lansky performance score of \>= 50 * Pediatric patients (age 5-17 years): A serum creatinine based on age/sex as follows (within 28 days prior to enrollment): * 2 to \< 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female) * 6 to \< 10 years (age): 1 mg/dL (male), 1 mg/dL (female) * 10 to \< 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female) * 13 to \< 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female) * \>= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment) OR a glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) * Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility * For adult patients (age 18 years or older) (within 28 days prior to enrollment): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. 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 * Total bilirubin =\< 2 x upper limit of normal (ULN) (within 28 days prior to enrollment) * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Aspartate aminotransferase (AST) =\< 3 x ULN (within 28 days prior to enrollment) * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Alanine aminotransferase (ALT) =\< 3 x ULN (within 28 days prior to enrollment) * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Shortening fraction of \>= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 28 days prior to enrollment) or ejection fraction of \>= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 28 days prior to enrollment) * Diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 28 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of \> 92% on room air * Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load Exclusion Criteria: * Patients with nodular lymphocyte predominant Hodgkin lymphoma * Patients with a history of active interstitial pneumonitis or interstitial lung disease * Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients * Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills * Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to \> 10 mg daily predniSONE for patients \>= 18 years or \> 0.5 mg/kg \[up to 10 mg/day\] for patients \< 18 years) or other immunosuppressive medications within 14 days prior to enrollment * Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=\< 10 mg daily for patients \>= 18 years or =\< 0.5 mg/kg \[up to 10 mg/day\] predniSONE equivalents) are permitted in the absence of active autoimmune disease * Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1 * Short term use of corticosteroids for premedication or treatment of an allergy or hypersensitivity is considered an acceptable use of corticosteroids. * Patients with peripheral neuropathy \> grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen * Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL * Prior solid organ transplant * Prior allogeneic stem cell transplantation * 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). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential * Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment * Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer * Men and women of childbearing potential (WOCBP) must use effective contraception during the study and for 2 months for WOCBP and 4 months for men, after last dose of brentuximab vedotin * WOCBP must continue contraception for a period of at least 5 months after the last dose of nivolumab * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
healthy Volunteers
false
maximum Age
60 Years
minimum Age
5 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive ABVD IV for an additional 2 cycles on study. Each cycle lasts 28 days and ABVD is administered on days 1 and 15 of each cycle in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Procedure: Computed Tomography
    4. Drug: Dacarbazine
    5. Drug: Doxorubicin Hydrochloride
    6. Other: Fludeoxyglucose F-18
    7. Procedure: Magnetic Resonance Imaging
    8. Procedure: Positron Emission Tomography
    9. Other: Questionnaire Administration
    10. Drug: Vinblastine Sulfate
    label
    Arm A (ABVD)
    type
    ACTIVE_COMPARATOR
  2. description
    Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes once during each treatment cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Drug: Brentuximab Vedotin
    4. Procedure: Computed Tomography
    5. Drug: Dacarbazine
    6. Drug: Doxorubicin Hydrochloride
    7. Other: Fludeoxyglucose F-18
    8. Procedure: Magnetic Resonance Imaging
    9. Biological: Nivolumab
    10. Procedure: Positron Emission Tomography
    11. Other: Questionnaire Administration
    12. Drug: Vinblastine Sulfate
    label
    Arm B (ABVD, brentuximab vedotin, nivolumab)
    type
    EXPERIMENTAL
  3. description
    See Detailed Description.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Procedure: Computed Tomography
    4. Drug: Cyclophosphamide
    5. Drug: Dacarbazine
    6. Drug: Doxorubicin Hydrochloride
    7. Drug: Etoposide
    8. Drug: Etoposide Phosphate
    9. Other: Fludeoxyglucose F-18
    10. Radiation: Involved-site Radiation Therapy
    11. Procedure: Magnetic Resonance Imaging
    12. Procedure: Positron Emission Tomography
    label
    Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    type
    EXPERIMENTAL
  4. description
    Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive brentuximab vedotin IV and nivolumab IV as in arm B followed by ISRT. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Drug: Brentuximab Vedotin
    4. Procedure: Computed Tomography
    5. Drug: Dacarbazine
    6. Drug: Doxorubicin Hydrochloride
    7. Other: Fludeoxyglucose F-18
    8. Radiation: Involved-site Radiation Therapy
    9. Procedure: Magnetic Resonance Imaging
    10. Biological: Nivolumab
    11. Procedure: Positron Emission Tomography
    12. Other: Questionnaire Administration
    label
    Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    type
    EXPERIMENTAL
  5. description
    Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive AVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, vinblastine IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Procedure: Computed Tomography
    4. Drug: Dacarbazine
    5. Drug: Doxorubicin Hydrochloride
    6. Other: Fludeoxyglucose F-18
    7. Procedure: Magnetic Resonance Imaging
    8. Procedure: Positron Emission Tomography
    9. Other: Questionnaire Administration
    10. Drug: Vinblastine Sulfate
    label
    Arm E (ABVD, AVD)
    type
    EXPERIMENTAL
  6. description
    Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive treatment as in arm B. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Drug: Brentuximab Vedotin
    4. Procedure: Computed Tomography
    5. Drug: Dacarbazine
    6. Drug: Doxorubicin Hydrochloride
    7. Other: Fludeoxyglucose F-18
    8. Procedure: Magnetic Resonance Imaging
    9. Biological: Nivolumab
    10. Procedure: Positron Emission Tomography
    11. Other: Questionnaire Administration
    12. Drug: Vinblastine Sulfate
    label
    Arm F (ABVD, brentuximab vedotin, nivolumab)
    type
    EXPERIMENTAL
  7. description
    Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive treatment and imaging, and may undergo blood sample collection as in arm C.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Procedure: Computed Tomography
    4. Drug: Cyclophosphamide
    5. Drug: Dacarbazine
    6. Drug: Doxorubicin Hydrochloride
    7. Drug: Etoposide
    8. Drug: Etoposide Phosphate
    9. Other: Fludeoxyglucose F-18
    10. Radiation: Involved-site Radiation Therapy
    11. Procedure: Magnetic Resonance Imaging
    12. Procedure: Positron Emission Tomography
    label
    Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    type
    EXPERIMENTAL
  8. description
    Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive treatment and imaging, and may undergo blood sample collection as in arm D.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Biological: Bleomycin Sulfate
    3. Drug: Brentuximab Vedotin
    4. Procedure: Computed Tomography
    5. Drug: Dacarbazine
    6. Drug: Doxorubicin Hydrochloride
    7. Other: Fludeoxyglucose F-18
    8. Radiation: Involved-site Radiation Therapy
    9. Procedure: Magnetic Resonance Imaging
    10. Biological: Nivolumab
    11. Procedure: Positron Emission Tomography
    12. Other: Questionnaire Administration
    label
    Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (ABVD, brentuximab vedotin, nivolumab)
    3. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    5. Arm E (ABVD, AVD)
    6. Arm F (ABVD, brentuximab vedotin, nivolumab)
    7. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    8. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    description
    Undergo blood sample 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 A (ABVD)
    2. Arm B (ABVD, brentuximab vedotin, nivolumab)
    3. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    5. Arm E (ABVD, AVD)
    6. Arm F (ABVD, brentuximab vedotin, nivolumab)
    7. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    8. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    description
    Given IV
    name
    Bleomycin Sulfate
    other Names
    1. Blanoxan
    2. BleMomycine
    3. Blenoxane
    4. Bleo-cell
    5. Bleo-S
    6. Bleocin
    7. Bleolem
    8. Bleomycin Sulfas
    9. Bleomycin Sulphate
    10. Bleomycini Sulfas
    11. Blexane
    12. Oil Bleo
    type
    BIOLOGICAL
  3. arm Group Labels
    1. Arm B (ABVD, brentuximab vedotin, nivolumab)
    2. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    3. Arm F (ABVD, brentuximab vedotin, nivolumab)
    4. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    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
  4. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (ABVD, brentuximab vedotin, nivolumab)
    3. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    5. Arm E (ABVD, AVD)
    6. Arm F (ABVD, brentuximab vedotin, nivolumab)
    7. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    8. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    description
    Undergo CT and/or PET-CT
    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
  5. arm Group Labels
    1. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    2. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Asta B 518
    4. B 518
    5. B-518
    6. B518
    7. Carloxan
    8. Ciclofosfamida
    9. Ciclofosfamide
    10. Cicloxal
    11. Clafen
    12. Claphene
    type
    DRUG
  6. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (ABVD, brentuximab vedotin, nivolumab)
    3. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    5. Arm E (ABVD, AVD)
    6. Arm F (ABVD, brentuximab vedotin, nivolumab)
    7. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    8. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    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
  7. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (ABVD, brentuximab vedotin, nivolumab)
    3. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    5. Arm E (ABVD, AVD)
    6. Arm F (ABVD, brentuximab vedotin, nivolumab)
    7. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    8. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    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
  8. arm Group Labels
    1. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    2. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    description
    Given IV
    name
    Etoposide
    other Names
    1. Demethyl Epipodophyllotoxin Ethylidine Glucoside
    2. EPEG
    3. Lastet
    4. Toposar
    5. Vepesid
    6. VP 16
    7. VP 16-213
    8. VP 16213
    9. VP-16
    10. VP-16-213
    11. VP-16213
    12. VP16
    type
    DRUG
  9. arm Group Labels
    1. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    2. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    description
    Given IV
    name
    Etoposide Phosphate
    other Names
    1. Etopophos
    type
    DRUG
  10. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (ABVD, brentuximab vedotin, nivolumab)
    3. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    5. Arm E (ABVD, AVD)
    6. Arm F (ABVD, brentuximab vedotin, nivolumab)
    7. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    8. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    description
    Undergo FDG-PET
    name
    Fludeoxyglucose F-18
    other Names
    1. 18FDG
    2. FDG
    3. Fludeoxyglucose (18F)
    4. fludeoxyglucose F 18
    5. Fludeoxyglucose F18
    6. Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
    7. Fluorodeoxyglucose F18
    type
    OTHER
  11. arm Group Labels
    1. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    2. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    3. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    description
    Undergo ISRT
    name
    Involved-site Radiation Therapy
    other Names
    1. ISRT
    type
    RADIATION
  12. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (ABVD, brentuximab vedotin, nivolumab)
    3. Arm C (ABVD, eBEACOPP or eBPDac, ISRT)
    4. Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
    5. Arm E (ABVD, AVD)
    6. Arm F (ABVD, brentuximab vedotin, nivolumab)
    7. Arm G (ABVD, eBEACOPP or eBPDac, ISRT)
    8. Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
    description
    Undergo MRI and/or PET-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
Study design
allocation
RANDOMIZED
intervention Model
SEQUENTIAL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
1875
type
ESTIMATED
Registered outcome plans (not posted results)
other Outcomes
  1. description
    Will be compared between a standard chemotherapy approach and an IO therapy approach within different age groups (ages 5-11 years, 12-21 years, 22-39 years, 40-60 years) using log-rank tests. Cox regression models will be constructed to evaluate the treatment effects for different age groups while considering the impact of other potentially prognostic variables including baseline demographics and clinical risk factors. PFS and corresponding confidence intervals for each age group will be estimated with the Kaplan-Meier method, overall and by treatment arms. In additional models, age may be evaluated as a continuous variable with potentially non-linear effects on PFS.
    measure
    PFS comparison between treatment arms for each age group
    time Frame
    Up to 12 years
  2. description
    The concordance and discordance of 5-PS visual PET assessment from rapid central review and local institutional review will be evaluated at each of the timepoints. Will collect and retrospectively review local vs. central review concordance rates. For discordant cases, will document the differences in treatments if only local review or only central review were performed
    measure
    Concordance and discordance of 5-point score (PS) visual PET assessments
    time Frame
    At baseline, post cycle 2, and at end of systemic therapy
  3. description
    The association between FDG PET parameters obtained by automated measurements using convolutional neural networks and PFS will be evaluated in this aim. The PET parameters of interest are total MTV and TLG, tumor standardized uptake value change. PET parameters will be obtained based on artificial intelligence (AI) based measurements. The effect of these PET measurements will be evaluated by Cox regression models.
    measure
    Association between FDG PET parameters obtained by automated measurements and PFS
    time Frame
    At baseline, post cycle 2, and at the end of therapy
  4. description
    Will compare AI derived automated quantitative FDG-PET measurement extraction and physician-based manual quantitative PET measurement with Spearman rank correlation coefficients for each extracted PET metric.
    measure
    Agreement between AI derived FDG-PET measurement extraction and physician-based manual quantitative PET measurement
    time Frame
    At baseline, post cycle 2, and at the end of therapy
  5. description
    Will be collected by PRO-CTCAE and Ped-PRO-CTCAE. The patient reported AEs will be compared to provider reported AEs reported descriptively.
    measure
    Incidence of patient reported adverse events and provider adverse event reporting
    time Frame
    Assessed up to 12 years
  6. description
    Will be evaluated by Chi-square tests or Fisher exact tests for sparse data. Will also calculate the area deprivation index (derived from patient-reported address and zip code to census block-group data for patients treated in the United States, and the Canadian Index of Multiple Deprivation for patients treated in Canada) and investigate its association with race/ethnicity and SDOH.
    measure
    Association between self-reported race/ethnicity and dimensional SDOH
    time Frame
    Assessed up to 12 years
  7. description
    The K-M curves will be presented together with p-values via log-rank tests across the different race/ethnicity groups for each treatment arm. Cox proportional hazard models to evaluate the relationship between race/ethnicity and post-relapse OS will be constructed.
    measure
    Post-relapse/post-progression OS by race/ethnicity and select SDOH measures
    time Frame
    Assessed up to 12 years
  8. description
    Will be evaluated for the first 450 eligible participants.
    measure
    Completion rate of PRO and health-related quality of life contact forms
    time Frame
    At 1 year off treatment
primary Outcomes
  1. description
    Will compare the PFS of RER patients randomized to immunotherapy (IO) therapy (brentuximab vedotin-nivolumab) against those randomized to standard therapy. PFS curves will be estimated separately by arm using Kaplan Meier methodology, and the test will be a 1-sided log-rank test between the (pooled) IO and standard arms, stratified according to the stratification factors at randomization and including all eligible and evaluable randomized patients.
    measure
    Progression-free survival (PFS) in rapid early responder (RER) patients
    time Frame
    From the time of randomization to the earliest time of disease relapse, progression, or death due to any cause, assessed up to 3 years after the randomization of the last patient or when reaching 124 events, whichever comes first
  2. description
    Will compare PFS among SER patients randomized to IO therapy and involved-site radiation therapy against arms containing standard therapy. PFS curves will be estimated separately by arm using Kaplan Meier methodology, and the test will be a 1-sided log-rank test between the (pooled) IO and standard arms, stratified according to the stratification factors at randomization and including all eligible and evaluable randomized patients.
    measure
    PFS in slow-early responder (SER) patients
    time Frame
    From the time of randomization to the earliest time of disease relapse, progression, or death due to any cause, assessed up to 3 years after the randomization of the last patient or when reaching 71 events, whichever comes first
secondary Outcomes
  1. description
    The non-inferiority of IO therapy to standard therapy will be tested in the randomized and eligible RER cohort using a confidence interval approach performed 12 years after the last patient not lost to follow-up has reached more than 12 years of follow-up (patients are followed up to 13 years).
    measure
    Overall survival (OS) in RER patients
    time Frame
    Time from randomization to death due to any cause, assessed up to 12 years after the last enrollment
  2. description
    Will be compared between a standard chemotherapy approach and an IO therapy approach among the SER patients.
    measure
    OS in SER patients
    time Frame
    Time from randomization to death due to any cause, assessed up to 12 years after the last enrollment
  3. description
    Will be based on a confidence interval approach conducted after the last patient not lost to follow-up has been followed for at least 12 years from randomization. Twelve-year OS and its corresponding 90% confidence interval will be estimated with the Kaplan-Meier method for each study arm within the entire randomized and evaluable trial population.
    measure
    OS for entire patient population
    time Frame
    Time from randomization to death due to any cause, assessed at 12 years after the last enrollment
  4. description
    Will be estimated in patients with favorable features at diagnosis. PFS and a corresponding confidence interval will be estimated using the Kaplan-Meier approach. PFS will also be compared between the (pooled) IO therapy and standard therapy arms using stratified log-rank tests within each cohort.
    measure
    PFS for favorable risk patients
    time Frame
    Up to 12 years
  5. description
    Will be estimated in patients with unfavorable features at diagnosis. PFS and a corresponding confidence interval will be estimated using the Kaplan-Meier approach. PFS will also be compared between the (pooled) IO therapy and standard therapy arms using stratified log-rank tests within each cohort.
    measure
    PFS for unfavorable risk patients
    time Frame
    Up to 12 years
  6. description
    PFS and a corresponding confidence interval will be estimated using the Kaplan-Meier approach. PFS will also be compared between the (pooled) IO therapy and standard therapy arms using stratified log-rank tests within each cohort.
    measure
    PFS for entire population
    time Frame
    Up to 12 years
  7. description
    Pooling IO treatment arms and standard treatment arms, EFS and corresponding confidence intervals will be estimated with the Kaplan-Meier approach for patients assigned versus (vs.) not assigned to receive radiaton therapy (RT), and compared using the log-rank test.
    measure
    Event-free survival (EFS)
    time Frame
    Time from randomization to the earliest of progression, relapse, second malignancy, or death due to any cause, assessed up to 12 years from last enrollment
  8. description
    Will use the American Society of Clinical Oncology and the Society for Immunotherapy of Cancer guidelines to capture immune-related AEs. Physician-reported treatment related AEs will be reported for all grades using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Rates of individual toxicities with grades greater or equal to 3 will be compared between the pooled IO and standard arms using exact binomial tests. The maximum grade for each toxicity will be recorded for each patient. The rates and confidence intervals for these toxicities will be provided. Comparison of AEs will also be conducted for physician-reported treatment-related AEs between RT and non-RT patients.
    measure
    Incidence of adverse events (AEs)
    time Frame
    Assessed up to 12 years from last enrollment
  9. description
    Targeted patient-reported AEs will be collected at each time point using the PRO-CTCAE for patients 7 years and older. For youth (7-17 years) the Pediatric PRO-CTCAE form will be used and for those 18 years and older adult the PRO-CTCAE form will be used. For information collected by each of the above forms, the scores for each attribute together with frequency, severity and/or interference will be presented descriptively using summary statistics at each assessment time. Additionally, the worst severity and/or interference over the entire course will be summarized. The changes among main time points will be calculated. The results will be provided for the whole population and compared between subpopulations by arms and by age groups. Regression models based on longitudinal measurements can be constructed by considering the following covariates besides age groups: baseline demographics, clinical risk factors, and study arms.
    measure
    Patient reported outcomes (PRO)-CTCAE
    time Frame
    Assessed up to 12 years from last enrollment
  10. description
    Will be measured by validated short forms from the Patient Reported Outcomes Measurement Information System initiatives. Domain scores will be converted to T-scores with an established standard deviation of 10 points with an average score normalized to 50 within the healthy adult population. The minimal clinically important difference (MCID) in these PRO measures has been accepted to be 2-3 points of the standard deviation (SD = 10) of the measure. To account for the dual primary PRO outcomes of fatigue and cognitive deficits, we will consider Bonferroni correction of p-values. Primary interests will be differences in T-scores between IO and chemotherapy arms at 1-year post completion of therapy.
    measure
    Patient-reported fatigue
    time Frame
    Baseline up to 1 year from end of study treatment
  11. description
    Will be measured by validated short forms from the Neuro-QoL initiative. Domain scores will be converted to T-scores with an established standard deviation of 10 points with an average score normalized to 50 within the healthy adult population. The MCID in these PRO measures has been accepted to be 2-3 points of the standard deviation (SD = 10) of the measure. To account for the dual primary PRO outcomes of fatigue and cognitive deficits, we will consider Bonferroni correction of p-values. Primary interests will be differences in T-scores between IO and chemotherapy arms at 1-year post completion of therapy.
    measure
    Patient-reported cognitive deficits
    time Frame
    Baseline up to 1 year from end of study treatment
  12. description
    Domain scores will be converted to T-scores with an established standard deviation of 10 points with an average score normalized to 50 within the healthy adult population. The MCID in these PRO measures has been accepted to be 2-3 points of the standard deviation (SD = 10) of the measure. To account for the dual primary PRO outcomes of fatigue and cognitive deficits, we will consider Bonferroni correction of p-values. Primary interests will be differences in T-scores between IO and chemotherapy arms at 1-year post completion of therapy.
    measure
    Patient-reported health-related quality of life
    time Frame
    Baseline up to 1 year from end of study treatment
Full study description
brief Summary
This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride 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. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.
detailed Description
PRIMARY OBJECTIVES: I. To compare the progression-free survival (PFS) of a standard chemotherapy approach versus an immunotherapy (IO) approach (brentuximab vedotin and nivolumab) in patients with newly diagnosed early stage classic Hodgkin lymphoma (cHL) who have a rapid early response (RER) as determined by position emission tomography post cycle 2 (PET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy. II. To compare the PFS of a standard chemotherapy approach versus an IO therapy approach (brentuximab vedotin and nivolumab) plus involved site radiation therapy (ISRT) in patients with newly diagnosed early stage cHL who have a slow early response (SER) as determined by PET2 after 2 cycles of ABVD chemotherapy. SECONDARY OBJECTIVES: I. To demonstrate non-inferiority of overall survival (OS) at 12 years of IO therapy versus standard therapy in early stage cHL patients who have a RER as determined by PET2 after 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy. II. To evaluate the overall survival (OS) at 12 years of IO therapy versus standard therapy in early stage cHL patients who have a SER as determined by PET2 after 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy. III. To demonstrate non-inferiority of overall survival (OS) at 12 years of IO therapy versus standard therapy in early stage cHL patients. IV. To evaluate in patients with newly diagnosed early stage cHL the PFS of a standard chemotherapy approach versus an IO therapy approach (brentuximab vedotin and nivolumab) in the overall cohort, in the favorable risk cohort, and in the unfavorable risk cohort. V. To evaluate the event-free survival (EFS) at 12 years of patients undergoing standard chemotherapy versus an IO therapy approach (brentuximab vedotin and nivolumab). VI. To compare the physician-reported treatment-related adverse event (AE) rates between a standard chemotherapy approach and an IO therapy approach (brentuximab vedotin and nivolumab) in patients with newly diagnosed early stage cHL. VII. To compare patient-reported adverse events using pediatric and adult versions of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), stratified by age groups, therapeutic arms, and receipt of radiation therapy (RT) over time. VIII. To evaluate changes in patient-reported fatigue, cognitive functioning, and health-related quality of life (HRQoL), e.g., emotional, physical, and role functioning, by treatment arm, using validated adult and pediatric measurement systems. IX. To evaluate self-reported late morbidities (e.g., cardiovascular, pulmonary and endocrine) over time for children, adolescents and adults undergoing standard chemotherapy versus an IO therapy approach (brentuximab vedotin and nivolumab) with and without RT using measures from the St. Jude Lifetime Cohort Study (SJLIFE). X. To evaluate fludeoxyglucose F-18 (FDG)-position emission tomography (PET) measurements of metabolic tumor burden (MTV and total lesion glycolysis \[TLG\]) at PET at baseline (PET1) as a predictive marker of PFS. XI. To evaluate the associations between race/ethnicity and key outcomes including early response to therapy, PFS and OS. EXPLORATORY OBJECTIVES: I. To evaluate the PFS of a standard chemotherapy approach versus an IO therapy approach (brentuximab vedotin and nivolumab) in patients with newly diagnosed early stage cHL across different age groups (ages 5-11 years, 12-21 years, 22-39 years, 40-60 years). II. To bank specimens for future correlative studies. III. To assess concordance and discordance of rapid central review and local institutional review of FDG PET 5-point score (5-PS; previously referred to as Deauville score) at baseline PET1, interim PET2 and end of systemic therapy PET-end of systemic therapy (EST) SER. IV. To assess the association between PFS and the quantitative FDG-PET/computed tomography (CT) parameters (PET MTV, TLG, delta-standardized uptake value \[SUV\] and PET SUV-based quantitative surrogates \[qPET\] of visual qualitative 5-PS) on measurements by automated measurements using convolutional neural networks (CNNs) through artificial-intelligence (AI) machine learning in the entire population. V. To assess the agreement between quantitative FDG-PET/CT parameters obtained using AI and those based on measurements by a trained imaging physician. VI. To compare patient-reported adverse events (via pediatric \[Ped\]-PRO-CTCAE and PRO-CTCAE) to provider adverse event reporting. VII. To evaluate the association between self-reported race/ethnicity and social determinants of health. VIII. To evaluate the associations between race/ethnicity and post-progression/post-relapse overall survival. IX. To evaluate the completion rates of PRO and health-related quality of life (HRQoL) contact forms at 1 year off treatment for the first 450 eligible patients. X. To collect contact information from participants for future re-contact. OUTLINE: Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride intravenously \[IV\] over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or magnetic resonance imaging (MRI) and are identified as RER or SER. Patients with a favorable risk status and RER are randomized to Arm A or Arm B. Patients with a favorable risk status and SER are randomized to Arm C or Arm D. Patients with an unfavorable risk status and RER are randomized to Arm E or Arm F. Patients with an unfavorable risk status and SER are randomized to Arm G or Arm H. ARM A (RER, FAVORABLE): Patients receive ABVD IV for an additional 2 cycles on study. Each cycle lasts 28 days and ABVD is administered on days 1 and 15 of each cycle in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial. ARM B (RER, FAVORABLE): Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes once during each treatment cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial. ARM C (SER, FAVORABLE): Patients receive either the eBEACOPP regimen (doxorubicin hydrochloride IV over 3-15 minutes on day 1, cyclophosphamide IV over 30-60 minutes on day 1, etoposide or etoposide phosphate IV over 2-4 hours on days 1-3, prednisone or prednisolone orally \[PO\] twice daily \[BID\] on days 1-14, procarbazine hydrochloride PO on days 1-7, bleomycin sulfate IV over at least 10 minutes on day 8, and vincristine sulfate IV on day 8 of each cycle) or the eBPDac regimen (doxorubicin hydrochloride IV 3-15 minutes on day 1, cyclophosphamide IV 30-60 minutes on day 1, etoposide or etoposide phosphate IV over 2-4 hours on days 1-3, prednisone or prednisolone PO BID on days 1-14, dacarbazine IV over 15-60 minutes on days 2 \& 3, bleomycin sulfate IV over at least 10 minutes on day 4, 5, 6, 7, or 8, vincristine sulfate IV on day 4, 5, 6, 7, or 8 of each cycle). Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Subsequently, patients undergo ISRT. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial. ARM D (SER, FAVORABLE): Patients receive brentuximab vedotin IV and nivolumab IV as in arm B followed by ISRT. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial. ARM E (RER, UNFAVORABLE): Patients receive AVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, vinblastine IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial. ARM F (RER, UNFAVORABLE): Patients receive treatment as in arm B. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial. ARM G (SER, UNFAVORABLE): Patients receive treatment and imaging, and may undergo blood sample collection as in arm C. ARM H (SER, UNFAVORABLE): Patients receive treatment and imaging, and may undergo blood sample collection as in arm D. After completion of study treatment, patients are followed up every 3 months for the first year, then every 6 months for the second and third year, then annually until 12 years from date of registration.
Source references
references
  1. 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
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      1. context
        Updated: April 16, 2025
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        April 16, 2025

    Preserved source evidence · Not medical advice