Active, not recruitingNCT03907488Updated Oct 1, 2026Results posted

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

A Phase 3 interventional study of Biospecimen Collection and Brentuximab Vedotin in Ann Arbor Stage III Hodgkin Lymphoma, Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma and Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 728 sites in 3 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-10-01.

Sponsored by National Cancer Institute (NCI) · Phase 3, Interventional, and Treatment

Updated Oct 1, 20261 site added1 site removedGo to Updates ↓

Phase: Phase 3
Study type: Interventional
Enrollment: 994
Allocation: Randomized
Ages: 12 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Ann Arbor Stage III Hodgkin Lymphoma
Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma
Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma
Ann Arbor Stage III Nodular Sclerosis Classic Hodgkin Lymphoma
Ann Arbor Stage IV Hodgkin Lymphoma
Ann Arbor Stage IV Lymphocyte-Depleted Classic Hodgkin Lymphoma
Ann Arbor Stage IV Mixed Cellularity Classic Hodgkin Lymphoma
Ann Arbor Stage IV Nodular Sclerosis Classic Hodgkin Lymphoma
Classic Hodgkin Lymphoma
Lymphocyte-Rich Classic Hodgkin Lymphoma

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Hodgkin Disease 885

In context

Hodgkin Disease

885 studies on the registry are indexed under Hodgkin Disease; 132 are open to participants now.

This study's enrollment of 994 is above the median of 44 across 726 interventional studies indexed under Hodgkin Disease.

Browse Hodgkin Disease studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 12 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 994 participants (actual)

Study arms

Experimental
Arm I (chemotherapy, nivolumab, radiation)
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.
Procedure: Biospecimen Collection · Procedure: Computed Tomography · Drug: Dacarbazine · Drug: Doxorubicin Hydrochloride · Biological: Filgrastim · Procedure: Magnetic Resonance Imaging · Biological: Nivolumab · Biological: Pegfilgrastim · Procedure: Positron Emission Tomography · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Radiation: Radiation Therapy · Drug: Vinblastine Sulfate
Experimental
Arm II (chemotherapy, brentuximab vedotin, radiation)
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.
Procedure: Biospecimen Collection · Drug: Brentuximab Vedotin · Procedure: Computed Tomography · Drug: Dacarbazine · Drug: Doxorubicin Hydrochloride · Biological: Filgrastim · Procedure: Magnetic Resonance Imaging · Biological: Pegfilgrastim · Procedure: Positron Emission Tomography · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Radiation: Radiation Therapy · Drug: Vinblastine Sulfate

Interventions

ProcedureBiospecimen Collection
Undergo peripheral blood collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
DrugBrentuximab Vedotin
Given IV
Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN 35, SGN-35, SGN35
ProcedureComputed Tomography
Undergo PET/CT or CT scan
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography
DrugDacarbazine
Given IV
Also known as: 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007
DrugDoxorubicin Hydrochloride
Given IV
Also known as: 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), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex
BiologicalFilgrastim
Given SC or IV
Also known as: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi, Filgrastim-ayow, Filgrastim-sndz, G-CSF, Granix, Neupogen, Neutroval, Nivestim, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, Releuko, rG-CSF, Tbo-filgrastim, Tevagrastim, XM02, Zarxio
ProcedureMagnetic Resonance Imaging
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
BiologicalNivolumab
Given IV
Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo
BiologicalPegfilgrastim
Given SC
Also known as: Cegfila, Dulastin, Dyrupeg, Filgrastim SD-01, filgrastim-SD/01, Fulphila, Fylnetra, G-Lasta, Grasustek, HSP-130, Jinyouli, Neulasta, Neulastim, Neupopeg, Nyvepria, PEG-filgrastim, Pegcyte, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Nyvepria, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim Biosimilar PF-06881894, Pegfilgrastim Biosimilar Udenyca, Pegfilgrastim Biosimilar Ziextenzo, Pegfilgrastim-apgf, Pegfilgrastim-bmez, Pegfilgrastim-cbqv, Pegfilgrastim-cegf, Pegfilgrastim-dyru, Pegfilgrastim-fpgk, Pegfilgrastim-gras, Pegfilgrastim-jmdb, Pegfilgrastim-pbbk, Pegfilgrastim-pelg, Pegfilgrastim-pelm, Pegylated G-CSF, Pegylated GCSF, Pegylated Granulocyte Colony Stimulating Factor, Pelgraz, Pelmeg, PF-06881894, SD-01, SD-01 sustained duration G-CSF, Stimufend, Tripegfilgrastim, Udenyca, Ziextenzo
ProcedurePositron Emission Tomography
Undergo PET/CT scan
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
OtherQuality-of-Life Assessment
Ancillary studies
Also known as: Quality of Life Assessment
OtherQuestionnaire Administration
Ancillary studies
RadiationRadiation Therapy
Receive radiation therapy
Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
DrugVinblastine Sulfate
Given IV
Also known as: 29060 LE, 29060-LE, Exal, Velban, Velbe, Velsar, VINCALEUKOBLASTINE

What researchers measure

Primary outcomes

Progression Free Survival (PFS)
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.
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

Overall Survival
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.
Time frame: From date of registration to two years or death.
Event-free Survival (EFS)
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.
Time frame: From date of registration to date of first occurrence of EFS event, assessed at 2 years
Number of Participants With of Adverse Events
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 2 years
Metabolic Complete Response Rate
This outcome measure will be reported by 11/5/2025.
Time frame: 4-8 weeks after last dose of study drug

Results

Posted Jun 12, 2025

Limitations and caveats

Our trial has several limitations, including the short follow-up time. Secondary analyses and subgroup analyses that involved specified stratification factors were preplanned, but these analyses did not have adequate statistical power.

Participant flow

Participant flow — Overall Study
Milestone	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)
Started	496	498
Completed	450	425
Not completed	46	73
Withdrew: Adverse event	20	20
Withdrew: Withdrawal by subject	9	13
Withdrew: Lack of efficacy	0	9
Withdrew: Death	3	8
Withdrew: Not protocol specified	5	8
Withdrew: Ineligible	9	15

Outcome measures

PrimaryProgression Free Survival (PFS)

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.

Time frame:: From date of registration to date of first observation of progressive disease, or death due to any cause, assessed at 2 years
Reported as:: Count of participants · Participants

Progression Free Survival (PFS)
Participants	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)
Progression Free Survival (PFS)	41	81

Statistical analysis

Arm I (Chemotherapy, Nivolumab, Radiation) vs Arm II (Chemotherapy, Brentuximab Vedotin, Radiation) · Log Rank · p = <0.005 (One sided P-value)

SecondaryOverall Survival

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.

Time frame:: From date of registration to two years or death.
Reported as:: Count of participants · Participants

Overall Survival
Participants	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)
Overall Survival	7	14

SecondaryEvent-free Survival (EFS)

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.

Time frame:: From date of registration to date of first occurrence of EFS event, assessed at 2 years
Reported as:: Count of participants · Participants

Event-free Survival (EFS)
Participants	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)
Event-free Survival (EFS)	52	91

SecondaryNumber of Participants With of Adverse Events

Only adverse events that are possibly, probably or definitely related to study drug are reported.

Time frame:: Up to 2 years
Reported as:: Count of participants · Participants

Number of Participants With of Adverse Events
Participants	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)
Abdominal distension	1	3
Abdominal pain	61	110
Activated partial thromboplastin time prolonged	2	3
Acute kidney injury	3	3
Adrenal insufficiency	2	0
Agitation	4	0
Akathisia	1	0
Alanine aminotransferase increased	163	209
Alkaline phosphatase increased	58	84
Allergic reaction	4	6
Allergic rhinitis	0	3
Alopecia	103	127
Amenorrhea	1	5
Amnesia	1	0
Anal fissure	0	1
Anal fistula	0	1
Anal hemorrhage	1	1
Anemia	198	222
Anorectal infection	1	0
Anorexia	61	107
Anosmia	3	1
Anxiety	20	30
Appendicitis	1	0
Arthralgia	65	60
Arthritis	3	0
Ascites	1	0
Aspartate aminotransferase increased	129	168
Ataxia	0	3
Atelectasis	1	1
Atrial fibrillation	1	1
Autoimmune disorder	1	0
Back pain	27	35
Bacteremia	0	2
Belching	3	1
Bladder infection	1	1
Bloating	7	18
Blood and lymphatic system disorders - Other, spec	3	5
Blood bicarbonate decreased	3	5
Blood bilirubin increased	14	14
Blood lactate dehydrogenase increased	18	25
Blurred vision	11	15
Bone pain	41	99
Brachial plexopathy	0	1
Breast pain	0	1
Bronchial infection	2	0
Bronchospasm	1	0
Bruising	2	8
Bullous dermatitis	0	1
Burn	0	1
Buttock pain	1	0
CD4 lymphocytes decreased	0	1
CPK increased	1	1
Cardiac arrest	0	2
Cardiac disorders - Other, specify	6	0
Cardiac troponin I increased	1	0
Cardiac troponin T increased	1	0
Catheter related infection	1	3
Cheilitis	1	0
Chest pain - cardiac	4	0
Chest wall pain	2	1
Chills	22	20
Cholesterol high	0	1
Chronic kidney disease	1	0
Cognitive disturbance	3	0
Colitis	6	6
Colonic obstruction	0	1
Concentration impairment	4	7
Confusion	3	2
Conjunctivitis	1	4
Conjunctivitis infective	0	2
Constipation	196	209
Cough	33	32
Creatinine increased	27	13
Cyanosis	1	0
Dehydration	14	32
Delirium	0	1
Depressed level of consciousness	1	2
Depression	10	10
Dermatitis radiation	0	2
Diarrhea	101	130
Disseminated intravascular coagulation	1	0
Dizziness	29	40
Dry eye	2	3
Dry mouth	19	32
Dry skin	15	17
Dysarthria	1	0
Dysesthesia	0	3
Dysgeusia	37	60
Dysmenorrhea	1	0
Dyspepsia	34	21
Dysphagia	8	7
Dysphasia	0	1
Dyspnea	43	58
Dysuria	3	1
Ear and labyrinth disorders - Other, specify	1	0
Ear pain	0	1
Eczema	3	7
Edema face	1	5
Edema limbs	17	17
Ejection fraction decreased	3	3
Electrocardiogram QT corrected interval prolonged	1	0
Electrocardiogram T wave abnormal	1	0
Endocrine disorders - Other, specify	9	0
Enterocolitis	2	1
Enterocolitis infectious	1	4
Eosinophilia	12	16
Epistaxis	10	16
Erectile dysfunction	2	0
Erythema multiforme	1	1
Erythroderma	1	0
Esophageal pain	1	0
Esophagitis	2	3
Extrapyramidal disorder	1	2
Eye disorders - Other, specify	3	3
Facial muscle weakness	1	0
Facial pain	1	4
Fall	5	9
Fatigue	232	246
Febrile neutropenia	28	33
Fecal incontinence	0	1
Fever	64	63
Fibrinogen decreased	2	0
Flank pain	1	3
Flashing lights	1	1
Flatulence	4	6
Floaters	0	1
Flu like symptoms	4	3
Flushing	10	3
Folliculitis	2	2
Fracture	0	1
GGT increased	4	4
Gait disturbance	0	2
Gastric hemorrhage	0	1
Gastritis	9	8
Gastroesophageal reflux disease	27	40
Gastrointestinal disorders - Other, specify	10	14
Gastrointestinal pain	1	0
Gastroparesis	0	1
General disorders and administration site conditio	7	6
Generalized edema	1	0
Generalized muscle weakness	16	25
Glucose intolerance	1	0
Glucosuria	2	2
Guillain-Barre syndrome	0	1
Gynecomastia	0	1
Headache	71	77
Heart failure	2	1
Hematuria	4	0
Hemolysis	1	0
Hemorrhoidal hemorrhage	1	0
Hemorrhoids	4	1
Hepatic failure	2	0
Hepatobiliary disorders - Other, specify	2	1
Herpes simplex reactivation	1	3
Hiccups	6	11
Hoarseness	0	4
Hot flashes	9	20
Hypercalcemia	6	10
Hyperglycemia	57	67
Hyperhidrosis	14	16
Hyperkalemia	5	4
Hyperlipidemia	0	1
Hypermagnesemia	4	3
Hypernatremia	1	5
Hyperphosphatemia	17	16
Hypertension	41	43
Hyperthyroidism	13	0
Hypertriglyceridemia	2	2
Hyperuricemia	6	9
Hypoalbuminemia	43	41
Hypocalcemia	34	35
Hypoglycemia	7	6
Hypokalemia	31	64
Hypomagnesemia	5	22
Hyponatremia	30	57
Hypoparathyroidism	1	0
Hypophosphatemia	11	19
Hypotension	18	18
Hypothyroidism	36	3
Hypoxia	3	3
INR increased	3	1
Ileus	0	4
Immune system disorders - Other, specify	1	1
Infections and infestations - Other, specify	18	12
Infusion related reaction	36	10
Infusion site extravasation	2	2
Injection site reaction	1	2
Injury, poisoning and procedural complications - O	1	0
Insomnia	30	54
Investigations - Other, specify	13	10
Irregular menstruation	4	5
Irritability	1	1
Joint range of motion decreased	0	2
Laryngopharyngeal dysesthesia	1	0
Lethargy	3	2
Leukocytosis	2	6
Libido decreased	6	3
Lip infection	3	0
Lipase increased	2	1
Localized edema	3	3
Lung infection	10	14
Lymph gland infection	1	0
Lymph node pain	1	3
Lymphocyte count decreased	109	114
Lymphocyte count increased	4	10
Malaise	8	3
Memory impairment	8	4
Menorrhagia	1	1
Metabolism and nutrition disorders - Other, specif	5	2
Mitral valve disease	1	0
Movements involuntary	1	2
Mucosal infection	1	1
Mucositis oral	109	100
Muscle cramp	14	19
Muscle weakness lower limb	5	7
Muscle weakness trunk	1	0
Muscle weakness upper limb	1	2
Musculoskeletal and connective tissue disorder -	5	6
Myalgia	54	58
Myositis	2	0
Nail changes	2	9
Nail discoloration	7	16
Nail infection	3	2
Nail ridging	1	1
Nasal congestion	6	12
Nausea	317	331
Neck edema	3	2
Neck pain	4	3
Neoplasms benign, malignant and unspecified (incl	2	0
Nervous system disorders - Other, specify	5	8
Neuralgia	2	3
Neutrophil count decreased	275	166
Non-cardiac chest pain	16	16
Oral dysesthesia	6	6
Oral hemorrhage	0	1
Oral pain	30	24
Pain	43	31
Pain in extremity	22	36
Palmar-plantar erythrodysesthesia syndrome	1	2
Palpitations	7	2
Pancreatic enzymes decreased	0	1
Pancreatitis	4	1
Papulopustular rash	4	3
Paresthesia	36	43
Paronychia	1	2
Paroxysmal atrial tachycardia	2	0
Pelvic pain	1	2
Penile infection	0	1
Pericardial effusion	1	0
Pericarditis	3	0
Peripheral motor neuropathy	21	36
Peripheral sensory neuropathy	141	268
Pharyngeal mucositis	1	0
Pharyngitis	0	1
Phlebitis	3	4
Photophobia	1	2
Photosensitivity	1	2
Platelet count decreased	53	89
Pleural effusion	2	1
Pleuritic pain	1	0
Pneumonitis	11	15
Postnasal drip	2	1
Presyncope	2	3
Productive cough	2	2
Proteinuria	2	2
Pruritus	48	25
Psychiatric disorders - Other, specify	1	3
Psychosis	0	1
Pulmonary edema	1	1
Rash acneiform	16	12
Rash maculo-papular	55	59
Rash pustular	0	1
Rectal fissure	0	1
Rectal hemorrhage	1	2
Rectal pain	1	4
Renal and urinary disorders - Other, specify	1	1
Respiratory failure	0	3
Respiratory, thoracic and mediastinal disorders -	3	6
Restrictive cardiomyopathy	1	0
Rhabdomyolysis	1	0
Rhinorrhea	6	8
Salivary duct inflammation	1	2
Scalp pain	1	0
Scrotal pain	0	1
Seizure	2	1
Sepsis	8	15
Serum amylase increased	1	0
Sinus bradycardia	1	3
Sinus disorder	0	1
Sinus tachycardia	17	25
Skin and subcutaneous tissue disorders - Other, sp	16	18
Skin hyperpigmentation	8	8
Skin hypopigmentation	3	0
Skin infection	6	10
Skin ulceration	0	1
Small intestinal obstruction	0	1
Sneezing	0	1
Somnolence	0	1
Sore throat	16	27
Spasticity	1	1
Stomach pain	10	10
Stroke	1	0
Superficial thrombophlebitis	3	3
Supraventricular tachycardia	0	1
Syncope	1	2
Tendon reflex decreased	1	1
Testicular pain	0	2
Thromboembolic event	12	10
Thrush	7	14
Thyroid stimulating hormone increased	28	1
Tinnitus	8	6
Tooth discoloration	0	1
Tooth infection	1	0
Toothache	3	2
Tracheal mucositis	0	1
Tracheitis	1	0
Tremor	4	3
Tumor lysis syndrome	1	1
Tumor pain	0	1
Typhlitis	0	3
Upper gastrointestinal hemorrhage	1	0
Upper respiratory infection	7	8
Urinary frequency	2	2
Urinary incontinence	1	1
Urinary retention	0	1
Urinary tract infection	7	12
Urinary tract pain	2	0
Urinary urgency	0	1
Urticaria	1	2
Vaginal discharge	2	0
Vaginal infection	2	4
Vascular access complication	1	2
Vascular disorders - Other, specify	3	1
Vasovagal reaction	0	1
Ventricular arrhythmia	1	1
Ventricular tachycardia	1	1
Vertigo	2	1
Vision decreased	3	0
Voice alteration	1	2
Vomiting	138	160
Watering eyes	1	5
Weight gain	13	8
Weight loss	25	71
Wheezing	2	1
White blood cell decreased	202	136
Wound infection	0	1

SecondaryMetabolic Complete Response Rate

This outcome measure will be reported by 11/5/2025.

Time frame:: 4-8 weeks after last dose of study drug

Results for this outcome have not been posted.

Adverse events

Collected over Up to 2 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm I (Chemotherapy, Nivolumab, Radiation)	7/487 (1.4%)	140/481 (29.1%)	468/481 (97.3%)
Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)	14/483 (2.9%)	18/476 (3.8%)	465/476 (97.7%)

Most frequent serious events

Showing 10 of 120

Most frequent serious events
Event	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)
Neutrophil count decreasedInvestigations	30/481	3/476
Febrile neutropeniaBlood and lymphatic system disorders	25/481	4/476
Infections and infestations-OtherInfections and infestations	18/481	0/476
SepsisInfections and infestations	11/481	6/476
White blood cell decreasedInvestigations	11/481	0/476
FeverGeneral disorders	10/481	0/476
Thromboembolic eventVascular disorders	10/481	0/476
VomitingGastrointestinal disorders	8/481	2/476
Platelet count decreasedInvestigations	7/481	1/476
DehydrationMetabolism and nutrition disorders	7/481	0/476

Most frequent other events

Showing 10 of 81

Most frequent other events
Event	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)
NauseaGastrointestinal disorders	338/481	354/476
FatigueGeneral disorders	283/481	277/476
Peripheral sensory neuropathyNervous system disorders	158/481	280/476
Neutrophil count decreasedInvestigations	277/481	171/476
AnemiaBlood and lymphatic system disorders	251/481	252/476
ConstipationGastrointestinal disorders	238/481	240/476
Alanine aminotransferase increasedInvestigations	180/481	232/476
White blood cell decreasedInvestigations	206/481	141/476
Aspartate aminotransferase increasedInvestigations	148/481	187/476
VomitingGastrointestinal disorders	156/481	182/476

Baseline characteristics

Modified intent to treat group, in participants deemed ineligible are excluded.

Age, Continuous
Age, Continuous(years)	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)	Total
Median	27.6 (12.0 to 83.7)	26.8 (12.0 to 81.7)	27 (12.0 to 83.7)

Age, Customized
Age, Customized(Participants)	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)	Total
Age, Stratified — 12-17	118	118	236
Age, Stratified — 18-60	321	318	639
Age, Stratified — >60	48	47	95

Sex: Female, Male
Sex: Female, Male(Participants)	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)	Total
Female	216	210	426
Male	271	273	544

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Arm I (Chemotherapy, Nivolumab, Radiation)	Arm II (Chemotherapy, Brentuximab Vedotin, Radiation)	Total
White	372	361	733
Black	58	56	114
Asian	11	17	28
Other or unknown	46	49	95
Hispanic	66	58	124

Study locations

728 sites

Children's Hospital of Alabama
Birmingham, Alabama 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233, United States
USA Health Strada Patient Care Center
Mobile, Alabama 36604, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama 36688, United States
Anchorage Associates in Radiation Medicine
Anchorage, Alaska 98508, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska 99508, United States
Alaska Oncology and Hematology LLC
Anchorage, Alaska 99508, United States
Alaska Women's Cancer Care
Anchorage, Alaska 99508, United States
Anchorage Oncology Centre
Anchorage, Alaska 99508, United States
Katmai Oncology Group
Anchorage, Alaska 99508, United States
Providence Alaska Medical Center
Anchorage, Alaska 99508, United States
Fairbanks Memorial Hospital
Fairbanks, Alaska 99701, United States
CTCA at Western Regional Medical Center
Goodyear, Arizona 85338, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona 85004, United States
Phoenix Childrens Hospital
Phoenix, Arizona 85016, United States
University of Arizona Cancer Center-Orange Grove Campus
Tucson, Arizona 85704, United States
Banner University Medical Center - Tucson
Tucson, Arizona 85719, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona 85719, United States
Mercy Hospital Fort Smith
Fort Smith, Arkansas 72903, United States
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas 71913, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas 72401, United States
Arkansas Children's Hospital
Little Rock, Arkansas 72202-3591, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205, United States
Kaiser Permanente-Anaheim
Anaheim, California 92806, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch, California 94531, United States
PCR Oncology
Arroyo Grande, California 93420, United States
Kaiser Permanente-Baldwin Park
Baldwin Park, California 91706, United States
Kaiser Permanente-Bellflower
Bellflower, California 90706, United States
Tower Cancer Research Foundation
Beverly Hills, California 90211, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California 91505, United States
City of Hope Comprehensive Cancer Center
Duarte, California 91010, United States
Kaiser Permanente Dublin
Dublin, California 94568, United States
Kaiser Permanente-Fontana
Fontana, California 92335, United States
Kaiser Permanente-Fremont
Fremont, California 94538, United States
Kaiser Permanente-Fresno
Fresno, California 93720, United States
Kaiser Permanente South Bay
Harbor City, California 90710, United States
Kaiser Permanente-Irvine
Irvine, California 92618, United States
UC San Diego Moores Cancer Center
La Jolla, California 92093, United States
Loma Linda University Medical Center
Loma Linda, California 92354, United States
Children's Hospital Los Angeles
Los Angeles, California 90027, United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California 90027, United States
Kaiser Permanente West Los Angeles
Los Angeles, California 90034, United States
Cedars-Sinai Medical Center
Los Angeles, California 90048, United States
Valley Children's Hospital
Madera, California 93636, United States
Fremont - Rideout Cancer Center
Marysville, California 95901, United States
Kaiser Permanente-Modesto
Modesto, California 95356, United States
Kaiser Permanente-Oakland
Oakland, California 94611, United States
Kaiser Permanente-Ontario
Ontario, California 91761, United States
Children's Hospital of Orange County
Orange, California 92868, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868, United States
Desert Regional Medical Center
Palm Springs, California 92262, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California 94304, United States
Kaiser Permanente - Panorama City
Panorama City, California 91402, United States
Kaiser Permanente-Richmond
Richmond, California 94801, United States
Kaiser Permanente-Riverside
Riverside, California 92505, United States
Kaiser Permanente Downtown Commons
Sacramento, California 95814, United States
Sutter Medical Center Sacramento
Sacramento, California 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817, United States
Kaiser Permanente-South Sacramento
Sacramento, California 95823, United States
Kaiser Permanente-San Diego Zion
San Diego, California 92120, United States
Rady Children's Hospital - San Diego
San Diego, California 92123, United States
Naval Medical Center -San Diego
San Diego, California 92134, United States
Kaiser Permanente-San Francisco
San Francisco, California 94115, United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158, United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California 95119, United States
Kaiser Permanente San Leandro
San Leandro, California 94577, United States
Pacific Central Coast Health Center-San Luis Obispo
San Luis Obispo, California 93401, United States
Kaiser Permanente-San Marcos
San Marcos, California 92078, United States
Kaiser San Rafael-Gallinas
San Rafael, California 94903, United States
Mission Hope Medical Oncology - Santa Maria
Santa Maria, California 93444, United States
Kaiser Permanente-Santa Rosa
Santa Rosa, California 95403, United States
Kaiser Permanente-South San Francisco
South San Francisco, California 94080, United States
Kaiser Permanente-Stockton
Stockton, California 95210, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California 90502, United States
Kaiser Permanente Medical Center-Vacaville
Vacaville, California 95688, United States
Kaiser Permanente-Vallejo
Vallejo, California 94589, United States
Kaiser Permanente-Walnut Creek
Walnut Creek, California 94596, United States
Presbyterian Intercommunity Hospital
Whittier, California 90602, United States
Kaiser Permanente-Woodland Hills
Woodland Hills, California 91367, United States
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado 80012, United States
The Medical Center of Aurora
Aurora, Colorado 80012, United States
Children's Hospital Colorado
Aurora, Colorado 80045, United States
UCHealth University of Colorado Hospital
Aurora, Colorado 80045, United States
Boulder Community Foothills Hospital
Boulder, Colorado 80303, United States
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado 80304, United States
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado 80907, United States
Rocky Mountain Cancer Centers-Penrose
Colorado Springs, Colorado 80907, United States
Kaiser Permanente-Franklin
Denver, Colorado 80205, United States
AdventHealth Porter
Denver, Colorado 80210, United States
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado 80218, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado 80218, United States
Saint Joseph Hospital - Cancer Centers of Colorado
Denver, Colorado 80218, United States
Mountain Blue Cancer Care Center - Swedish
Englewood, Colorado 80113, United States
Swedish Medical Center
Englewood, Colorado 80113, United States
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado 81501, United States
Banner North Colorado Medical Center
Greeley, Colorado 80631, United States
Kaiser Permanente-Rock Creek
Lafayette, Colorado 80026, United States
CommonSpirit Saint Anthony Hospital Cancer Center
Lakewood, Colorado 80228, United States
Rocky Mountain Cancer Centers-Littleton
Littleton, Colorado 80120, United States
AdventHealth Littleton
Littleton, Colorado 80122, United States

Showing the first 100 of 728 sites across 3 countries.

References and documents

Publications

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. PubMed 42577949 ↗
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. PubMed 42526889 ↗
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. PubMed 41512237 ↗
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. PubMed 39413375 ↗
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. PubMed 38945791 ↗
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. PubMed 37505794 ↗

Study documents

Protocol and statistical analysis plan · Sep 2, 2023
Informed consent form · Sep 2, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Updates

2 registry updates since Sep 25, 2026

Sites

1 site added, 1 site removed

Show site

Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States

Show 1 removed

West Virginia University Charleston Division · Charleston, United States

Oct 1, 2026

Show all 2 updates

Oct 1, 2026
1 site added, 1 site removed
Show site
- Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States
Show 1 removed
- West Virginia University Charleston Division · Charleston, United States
Sep 30, 2026
Minor edits only
+ 3 other changes: registry notes, verification date and references

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03907488
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Apr 9, 2019
Start date: Aug 29, 2019
Primary completion: Mar 31, 2024
Completion: Mar 28, 2027 (estimated)
Results posted: Jun 12, 2025
Last update: Oct 1, 2026

Study contacts

Alex F Herrera

principal investigator · SWOG Cancer Research Network

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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