Brentuximab Vedotin and Nivolumab in Treating Patients With Early Stage Classic Hodgkin Lymphoma
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)
2 other identifiers
interventional
155
1 country
17
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2018
Longer than P75 for phase_2
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 6, 2018
CompletedFirst Posted
Study publicly available on registry
October 19, 2018
CompletedStudy Start
First participant enrolled
November 28, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 23, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 23, 2024
CompletedNovember 6, 2024
November 1, 2024
6.1 years
August 6, 2018
November 5, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
18-month Progression-free survival (PFS) for each arm of therapy
Will be estimated using the method of Kaplan and Meier.
Up to 18 months
Secondary Outcomes (5)
Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
Up to 3 years
Scores from European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire C30, version 3 (EORTC-C30) for each arm of therapy
Up to 3 years
Positron emission tomography/computed tomography-2 negativity rate
After 2 courses of ABVD (each course is 28 days)
3-year PFS for each arm of treatment
Up to 3 years
Overall survival for each arm of treatment
Up to 3 years
Study Arms (3)
Group I 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.
Group I Arm B (ABVD, nivolumab)
EXPERIMENTALPatients 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 (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.
Interventions
Given IV
Given IV
Given IV
Given IV
Ancillary studies
Given IV
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (17)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
City of Hope Medical Center
Duarte, California, 91010, United States
University of California San Diego
San Diego, California, 92103, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Massachusetts General Hospital
Charlestown, Massachusetts, 02129, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Related Publications (1)
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.
PMID: 40135712DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alex F Herrera
City of Hope Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 6, 2018
First Posted
October 19, 2018
Study Start
November 28, 2018
Primary Completion
December 23, 2024
Study Completion
December 23, 2024
Last Updated
November 6, 2024
Record last verified: 2024-11