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Ann Arbor Stage I Hodgkin LymphomaPhase 2NCT03712202

Brentuximab Vedotin and Nivolumab in Treating Patients With Early Stage Classic Hodgkin Lymphoma

A Phase 2 study testing Bleomycin, Brentuximab Vedotin and Dacarbazine in people with Ann Arbor Stage I Hodgkin Lymphoma and Ann Arbor Stage I Mixed Cellularity Classic Hodgkin Lymphoma, run by City of Hope Medical Center at 17 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
Bleomycin, Brentuximab Vedotin and Dacarbazine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
159 participants
Where
17 sitesUnited States
Study dates
28 Nov 2018to 21 May 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative.
  • Assent, when appropriate, will be obtained per institutional guidelines.
  • Eastern Cooperative Oncology Group (ECOG) =< 2.
  • Histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) by current World Health Organization classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, or classical Hodgkin lymphoma, NOS [not otherwise specified]) at local enrolling center. Nodular lymphocyte-predominant Hodgkin lymphoma is excluded
  • Stage IA, IB, IIA, or IIB cHL by Cotswold modified Ann Arbor staging done prior to any treatment with ABVD.
  • Must have prior to standard of care ABVD treatment at least one lesion that is > 1.5 cm in the longest diameter on cross-sectional imaging and measureable in two perpendicular dimensions on CT and fludeoxyglucose (FDG) avid by PET.

Who cannot join

  • Patients must be naive in terms of any prior therapy for Hodgkin lymphoma (including immunotherapy, chemotherapy or radiation therapy) with the exception that they may have received up to 2 cycles of ABVD as standard of care therapy prior to enrollment, as long as they can start protocol therapy (therapy administered in Arms A, B1/B2, or C) within timelines specified by the trial.
  • Peripheral sensory neuropathy > grade 1 or any peripheral motor neuropathy.
  • History of another primary malignancy that has not been in remission for at least 3 years. (The following are exempt from the 3-year limit: nonmelanoma skin cancer, fully excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolau [PAP] smear)
  • Known cerebral/meningeal disease.
  • History of progressive multifocal leukoencephalopathy (PML).
  • Known history of pancreatitis.
Show all 16Show fewer
  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association class III-IV within 6 months prior to enrollment
  • Uncontrolled cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 45%, coronary artery disease, or arrhythmias.
  • Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin, nivolumab, or any component of ABVD.
  • Known active infection with hepatitis B or hepatitis C. Patients who are hepatitis B carriers can enroll if have a negative hepatitis B polymerase chain reaction (PCR) DNA test and are on hepatitis B suppressive medication management with entecavir or lamivudine. Patients with past active hepatitis C virus (HCV) infection are eligible if they are PCR negative after curative therapy. Testing to be done only in patients suspected of having infections or exposures.
  • Known active infection with human immunodeficiency virus (HIV). Patients who are HIV positive can enroll if CD4 count is > 200/uL and have an undetectable or unquantifiable HIV viral load within 28 days of enrollment, have concurrent management with infectious disease specialists, and are on stable combination antiretroviral therapy. Participants are required to be on antiretroviral regimens that are in accordance with the current International acquired immune deficiency syndrome (AIDS) Society guidelines concurrently with chemotherapy. The specific agents are at the discretion of the Investigator and the use of investigational agents currently available on an expanded access basis is allowed. Use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) or ritonavir (includes Norvir or Kaletra), Cobicistat, Didanosine (Videx or Videx EC), or similar potent CYP3 inhibitors are prohibited. In order to be eligible, participants taking zidovudine or ritonavir, Cobicistat, Didanosine, or other CYP3 inhibitors must change to a different regimen 7 days prior to therapy initiation. Changes to highly active antiretroviral therapy (HAART) therapy during the study may be made if medically necessary (toxicity, failure of regimen, etc.). Participants must be on HAART for at least 7 days prior to therapy. HIV testing to be done only in patients suspected of having infections or exposures
  • Subjects with active interstitial pneumonitis.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Females only: pregnant or breastfeeding.
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Massachusetts General Hospital

    Charlestown, Massachusetts, 02129

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • City of Hope Medical Center

    Duarte, California, 91010

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Sarah Cannon Cancer Center

    Nashville, Tennessee, 37203

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • University of California San Diego

    San Diego, California, 92103

Other trials in United States

About this study

Official title: A Phase 2 Front-Line PET/CT-2 Response-Adapted Brentuximab Vedotin and Nivolumab Incorporated and Radiation-Free Management of Early Stage Classical Hodgkin Lymphoma (cHL)

This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine the 18-month progression free survival (PFS) for each arm of therapy stratified by positron emission tomography (PET)/computed tomography (CT)-2 response.

SECONDARY OBJECTIVES:

  1. Assess safety, tolerability, and quality of life (QOL) for each arm of therapy.

II. Measure PET/CT-2 negativity rate after 2 lead-in cycles of standard of care doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD).

III. Evaluate the 3-year PFS and overall survival (OS) for each arm of treatment.

EXPLORATORY OBJECTIVES:

  1. Evaluate if a baseline antitumor immune response, as assessed by a Nanostring gene panel, correlates with PFS.

II. Evaluate if minimal residual disease (MRD) status, as monitored by cancer personalized profiling by deep sequencing (CAPP-Seq) of circulating tumor (ct) deoxyribonucleic acid (DNA), can be correlated with PFS.

OUTLINE: Patients are assigned to 1 of 2 groups based on their PET/CT-2 scans.

GROUP I (PET/CT-2 NEGATIVE): Patients without bulky disease are randomized to either Arm A or B and patients with bulky disease are assigned to Arm B.

ARM A: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

GROUP II (PET/CT-2 POSITIVE): Patients receive doxorubicin IV, vinblastine IV, dacarbazine, IV and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients that are PET/CT negative receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.

Being tested
Bleomycin, Brentuximab Vedotin, Dacarbazine, Doxorubicin, Nivolumab
Medical subject headings
Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BleomycinDrug

    Also called BLEO, BLM

    Given IV

  • Brentuximab VedotinDrug

    Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35

    Given IV

  • DacarbazineDrug

    Also called 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine

    Given IV

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • VinblastineDrug

    Also called Vincaleucoblastine, VLB

    Given IV

Study groups in NCT03712202
Study groupRoleWhat they receive
Arm A (brentuximab vedotin, nivolumab)ExperimentalPatients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Brentuximab Vedotin; Biological: Nivolumab; Other: Quality-of-Life Assessment
Arm B1 (ABVD, nivolumab) for non-bulky patientsExperimentalPatients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Bleomycin; Drug: Dacarbazine; Drug: Doxorubicin; Biological: Nivolumab; Other: Quality-of-Life Assessment; Drug: Vinblastine
Arm B2 (ABVD, nivolumab) for bulky patientsExperimentalPatients with bulky diseases at diagnosis receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Bleomycin; Drug: Dacarbazine; Drug: Doxorubicin; Biological: Nivolumab; Other: Quality-of-Life Assessment; Drug: Vinblastine
Arm C (AVD, brentuximab vedotin, nivolumab)ExperimentalPatients receive doxorubicin IV, vinblastine IV, dacarbazine, IV and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients that are PET/CT negative receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Brentuximab Vedotin; Drug: Dacarbazine; Drug: Doxorubicin; Other: Quality-of-Life Assessment; Drug: Vinblastine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 18-month Progression-free Survival (PFS) for Each Arm of Therapy

    Progression-free survival (PFS) was estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates was constructed based on the log-log transformation.

    Measured: Up to 18 months

Secondary outcomes (2)

  1. Number of Patients Experiencing Grade 3-5 Adverse Events Related to Study Treatment

    Toxicities were recorded and graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The events are possible, probable, or definite attribution to the study treatment.

    Measured: Up to 4 years

  2. 2-year Progression-free Survival (PFS) for Each Arm of Therapy

    Progression-free survival (PFS) was estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates was constructed based on the log-log transformation.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2018
  2. Study start28 Nov 2018
  3. Primary completion30 Nov 2024
  4. Study completion21 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
159 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03712202
Sponsor's protocol ID
18157
Other IDs
NCI-2018-01592, 18157
Status last verified
Oct 2026
First submitted
6 Aug 2018
Last updated
29 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

    PubMed 40135712

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bleomycin, Brentuximab Vedotin and Dacarbazine in people with Ann Arbor Stage I Hodgkin Lymphoma and Ann Arbor Stage I Mixed Cellularity Classic Hodgkin Lymphoma, run by City of Hope Medical Center at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

18-month Progression-free Survival (PFS) for Each Arm of Therapy (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03712202, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.

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