Brentuximab Vedotin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Stage II-IV Hodgkin Lymphoma

A Phase II Trial of Sequential SGN-35 Therapy With Adriamycin, Vinblastine, and Dacarbazine (S-AVD) for Older Patients With Untreated Hodgkin Lymphoma

This phase II trial studies how well giving brentuximab vedotin together with combination chemotherapy works in treating older patients with previously untreated stage II-IV Hodgkin lymphoma (HL). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine (AVD), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin, doxorubicin hydrochloride, vinblastine, and dacarbazine together may kill more cancer cells.

Study Overview

• Status: Completed
• Conditions: Stage III Adult Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma
• Intervention / Treatment: Procedure: quality-of-life assessment; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography; Drug: doxorubicin hydrochloride; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Drug: dacarbazine; Drug: brentuximab vedotin; Drug: vinblastine; Genetic: DNA analysis; Genetic: RNA analysis; Genetic: polymorphism analysis

Detailed Description

LEAD IN: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

AVD CHEMOTHERAPY: Patients then receive doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients achieving CR receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60611
      • NorthwesternU
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7835
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan- Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Previously untreated classical Hodgkin lymphoma (i.e., nodular sclerosis, mixed cellularity, lymphocyte depleted, lymphocyte-rich, and not otherwise specified [NOS]); nodular lymphocyte predominant Hodgkin lymphoma is not eligible
• Stage II, III, and IV disease by Ann Arbor classification
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Patients must have bi-dimensional measurable disease documented in the lymphoma baseline tumor assessment form within 30 days prior to registration (at least 1.5 cm); patients with non-measurable disease in addition to measurable disease must have been assessed within 60 days prior to registration
• Patients must have a bone marrow biopsy (bilateral preferred, unilateral acceptable) within 60 days prior to registration
• Patients must have a multi gated acquisition scan (MUGA) or echocardiogram within 60 days prior to study registration and the ejection fraction must be >= 45%
• Absolute neutrophil count (ANC) > 1000/mm^3
• Platelet count > 75,000/mm^3
• Creatinine < 2.5 mg/dl
• Bilirubin < 3.0 mg/dl
• Patients with documented marrow involvement by lymphoma at the time of registration are not required to meet the above hematologic parameters
• Patients must not have received prior chemotherapy or radiation therapy for the treatment of Hodgkin lymphoma
• Both females and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
• Patients must sign the informed consent form before registration

Exclusion Criteria:

• Previous treatment with brentuximab vedotin or any other prior anti-CD30-based antibody therapy
• 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: early stage [stage I or II] breast cancer treated with surgery and radiation +/- hormones [without adjuvant chemotherapy], non-melanoma 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 Papanicolaou test [PAP smear])
• Known cerebral/meningeal disease
• Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 1 week prior to first dose
• Patients with hepatitis B surface antigen (HBsAg) positive hepatitis B virus (HBV) infection; patients with prior history of hepatitis B infection, but immune, with only Immunoglobulin G (IgG) hepatitis core antibody + (HBcAb +) must receive anti-viral prophylaxis (e.g., lamivudine 100mg orally [po] daily) for at least 1 week prior to cycle 1 and throughout induction and continuation therapy and for at least 6 months after the last brentuximab vedotin dose; in addition, consultation with a hepatologist is recommended
• Patients with a known hypersensitivity to any excipient contained in the drug formulation
• Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (antibody-drug conjugate and combination chemo); LEAD-IN: Patients receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. AVD CHEMOTHERAPY: Patients then receive doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving CR receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Radiation: fludeoxyglucose F 18; Correlative studies; Other Names: 18FDG; FDG; Procedure: positron emission tomography; Correlative studies; Other Names: PET; FDG-PET; PET scan; tomography, emission computed; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM; Adriamycin PFS; Adriamycin RDF; ADR; Adria; Other: laboratory biomarker analysis; Optional correlative studies; Other: immunohistochemistry staining method; Optional correlative studies; Other Names: immunohistochemistry; Drug: dacarbazine; Given IV; Other Names: DIC; DTIC; DTIC-Dome; Drug: brentuximab vedotin; Given IV; Other Names: SGN-35; anti-CD30 ADC SGN-35; anti-CD30 antibody-drug conjugate SGN-35; antibody-drug conjugate SGN-35; Drug: vinblastine; Given IV; Other Names: Velban; Velsar; VLB; Genetic: DNA analysis; Optional correlative studies; Genetic: RNA analysis; Optional correlative studies; Genetic: polymorphism analysis; Optional correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission Rate After Chemotherapy	The primary objective of this study is to evaluate the complete remission rate among older patients with HL receiving sequential brentuximab vedotin therapy with AVD chemotherapy	after completion of AVD chemotherapy and prior to SGN-35 consolidation, approximately 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate After 2 Cycles of SGN-35	The incidence of overall response rate to induction SGN-35 will be reported for the initial 22 patients where PET is being employed.	2 cycles of SGN-35 lead-in therapy, approximately 42 days
Complete Remission Rate Following 2 Cycles of SGN-35	The incidence of CR rate to induction SGN-35 will be reported for the initial 22 patients where PET is being employed	2 cycles of lead-in SGN-35, approximately 42 days
Safety of Sequential SGN-35/AVD/SGN-35 Therapy	Detailed examination of Averse Events, laboratory test results, vital signs or other physical findings. Below we have summarized the top 10 most common Grade 3 and Grade 4 related adverse events. Please see the Adverse Events section of this record for a full listing of Adverse Events.	From time of treatment to 30 days after discontinuation of study treatment
2-year Progression Free Survival	Progression Free Survival (PFS) is defined as lymphoma progression or death from any cause. This outcome measure is the percentage of patients that have not progressed at 2 years from time of registration.	2 years from time of registration to study
Overall Survival Following SGN-35/AVD Sequential Therapy	Defined as the percentage of patients that are alive 2 years after registration.	up to 2 years from the time of registration
2 Year Event-Free Survival	An event is defined as treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death. This outcome measure is reported as the percentage of patient that did not have an event at 2 years from registration.	From registration until treatment failure, up to 2 years
Freedom From Progression	Measured from the time of study entry to progression of disease. Other causes of treatment failure are not include in freedom from progression.	from baseline to end of study, approximately 4 years
Patient Reported Outcomes for Symptoms and Quality of Life	Evaluate patient reported outcomes at baseline and during treatment to determine potential symptom palliation, treatment-related symptoms, and overall health-related quality of life. The Function Assessment of Cancer Therapy for Lymphoma (FACT-Lym) scale has a range of 0(minimum score) to 168 (maximum score). Higher scores indicate a better outcome. The mean scores for each timepoint are reported below.	Baseline and AVD Cycle 1, a total of 6 weeks
Association Between Cumulative Illness Rating Scale (CIRS) With Outcomes	Number of co-morbidities collected for each patient at baseline and at the end of completion of all therapy utilizing the Cumulative Illness Rating Scare (CIRS). For binary outcomes such as CR, logistic regression will be used to assess the relationship with CIRS score; for time-to-event outcomes, the method of Kalan Meier and the log rank test will be used. The minimum score of the CIRS is 0 and the maximum score is 56. High Scores on the CIRS scale indicate that the patient has more severe comorbidities	approximately 2 years from treatment start

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Seagen Inc.; Robert H. Lurie Cancer Center
• Investigators: Principal Investigator: Leo Gordon, MD, Northwestern University

Publications and helpful links

General Publications

• Evens AM, Advani RH, Helenowski IB, Fanale M, Smith SM, Jovanovic BD, Bociek GR, Klein AK, Winter JN, Gordon LI, Hamlin PA. Multicenter Phase II Study of Sequential Brentuximab Vedotin and Doxorubicin, Vinblastine, and Dacarbazine Chemotherapy for Older Patients With Untreated Classical Hodgkin Lymphoma. J Clin Oncol. 2018 Oct 20;36(30):3015-3022. doi: 10.1200/JCO.2018.79.0139. Epub 2018 Sep 4.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): April 6, 2017
• Study Completion (Actual): May 26, 2020

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: November 17, 2011
• First Posted (Estimated): November 22, 2011

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Hodgkin Disease; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Azoles; Cytological Techniques; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Triazenes; Imidazoles; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Chemistry Techniques, Analytical; Spectrum Analysis; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Aminoglycosides; Deoxyglucose; Deoxy Sugars; Daunorubicin; Histocytochemistry; Histological Techniques; Immunologic Techniques; Genetic Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; DNA Fingerprinting; Brentuximab Vedotin; Fluorodeoxyglucose F18; Doxorubicin; Dacarbazine; Vinblastine; Magnetic Resonance Spectroscopy; Immunohistochemistry; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; Amplified Fragment Length Polymorphism Analysis
• Other Study ID Numbers: NU 11H01; NCI-2011-00684 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); STU00046908 (Other Identifier: Northwestern University IRB)