A Study of Brentuximab Vedotin With Hodgkin Lymphoma (HL) and CD30-expressing Peripheral T-cell Lymphoma (PTCL)

A Phase 2 Open-label Study of Brentuximab Vedotin in Front-line Therapy of Hodgkin Lymphoma (HL) an dCD30-expressing Peripheral T-cell Lymphoma (PTCL) in Older Patients or Patients With Significant Comorbidities Ineligible for Standard Chemotherapy

This trial will study brentuximab vedotin to find out whether it is an effective treatment for Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL). Participants in this study will be older or will have other conditions that make them unable to have standard chemotherapy treatment. The study will look at brentuximab vedotin alone and combined with other drugs.

Study Overview

• Status: Completed
• Conditions: Hodgkin Disease; Peripheral T Cell Lymphoma
• Intervention / Treatment: Drug: brentuximab vedotin; Drug: dacarbazine; Drug: bendamustine; Drug: nivolumab

Detailed Description

This study is designed to evaluate the efficacy and tolerability of brentuximab vedotin as monotherapy and in combination with other agents as frontline therapy. There are 6 parts of the study. The population to be studied includes treatment-naïve patients with classical Hodgkin lymphoma (HL) or treatment-naïve patients with CD30-expressing peripheral T-cell lymphoma (PTCL).

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • University of Alberta / Cross Cancer Institute
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre - Victoria Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H1T 2M4
      • CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H4A 3J1
      • Royal Victoria Hospital, McGill University Health Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36604
      • University of South Alabama - Mitchell Cancer Institute
  • Alaska
    • Anchorage, Alaska, United States, 99503
      • Alaska Urological Institute
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85710
      • Arizona Oncology Associates, PC - HOPE
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center / University of Arizona
  • Arkansas
    • Springdale, Arkansas, United States, J. Thaddeus Beck
      • Highlands Oncology Group
  • California
    • Burbank, California, United States, 91505
      • Providence St Joseph Medical Center
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Pomona, California, United States, 91767
      • Wilshire Oncology Medical Group Inc.
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
  • Florida
    • Trinity, Florida, United States, 34655
      • Florida Cancer Affiliates
  • Georgia
    • Columbus, Georgia, United States, 31904
      • IACT Health
    • Sandy Springs, Georgia, United States, 30341
      • Georgia Cancer Specialists / Northside Hospital Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists / Advocate Lutheran General Hospital
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Networks LLC
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute / Wayne State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology P.A.
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center/ Carol G. Simon Cancer Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, P.C.
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center / University of Rochester Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
    • Columbus, Ohio, United States, 43210
      • James Cancer Hospital / Ohio State University
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
    • Tigard, Oregon, United States, 97223
      • Northwest Cancer Specialists, P.C.
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health
  • Texas
    • Arlington, Texas, United States, 76012
      • Arlington Cancer Center
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford
    • Dallas, Texas, United States, 75231
      • Texas Oncology - Presbyterian Cancer Center Dallas
    • Denton, Texas, United States, Kurkul
      • Texas Oncology - Denton South
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology - Fort Worth 12th Avenue
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center / University of Texas
    • Longview, Texas, United States, 75601
      • Texas Oncology - Longview
    • McAllen, Texas, United States, 78503
      • Texas Oncology - McAllen
    • Round Rock, Texas, United States, 78665
      • Texas Oncology - Seton Williamson
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center
    • Salem, Virginia, United States, 24153
      • Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
    • Winchester, Virginia, United States, 22601
      • Shenandoah Oncology P.C.
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute/Virginia Mason Medical Center
    • Wenatchee, Washington, United States, 98821
      • Wenatchee Valley Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Carbone Cancer Center / University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Parts A, B, C, and D: 60 years of age or older
• Treatment-naive patients with histopathological diagnosis of classical Hodgkin lymphoma (Parts A, B, C, D, and E)
• Treatment-naive patients with CD30-expressing PTCL (Part F)
• Ineligible for or have declined initial conventional combination chemotherapy for HL (Parts A, B, C, and D)

• Unsuitable or unfit for initial conventional combination chemotherapy for HL (Part E) or CD30-expressing PTCL due to the presence of comorbidity-factors, as documented by:

  • A CIRS score of 10 or greater
  • Requiring assistance with or dependence on other for any instrumental activities of daily living (IADLs)
• Measurable disease of at least 1.5 cm as documented by radiographic technique
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3 (Parts, A, B, C, E, and F) or less than or equal to 2 (Part D)

Exclusion Criteria:

• Symptomatic neurologic disease compromising IADLs or requiring medication
• History of progressive multifocal leukoencephalopathy
• Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of brentuximab vedotin
• Concurrent use of other investigational agents
• Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy not completed 4 weeks prior to first dose of study drug
• History of another malignancy within 1 year before first dose of study drug (Parts E and F only)

• Part D only:

  • Received any prior immune-oncology therapy
  • History of known or suspected autoimmune disease
  • Prior allogeneic stem cell transplant
  • History of cerebral vascular event within 6 months of first dose of study drug
  • Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicology
  • Known history of pancreatitis

• Parts D, E, and F only:

  • Known cerebral/meningeal disease related to the underlying malignancy
  • Systemic treatment with corticosteroids or other immunosuppressive medications within 1 week of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Brentuximab Vedotin in HL Patients	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35
Experimental: Part B: Brentuximab Vedotin + Dacarbazine in HL Patients	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35; Drug: dacarbazine; 375 mg/m^2 every 3 weeks by IV infusion
Experimental: Part C: Brentuximab Vedotin + Bendamustine in HL Patients	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35; Drug: bendamustine; 70 mg/m^2 by IV infusion on Days 1 and 2 of 3-week cycle
Experimental: Part D: Brentuximab Vedotin + Nivolumab in HL Patients	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35; Drug: nivolumab; 3 mg/kg every 3 weeks by IV infusion
Experimental: Part E: Brentuximab Vedotin in HL Patients	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35
Experimental: Part F: Brentuximab Vedotin in PTCL Patients	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) According to the Revised Response Criteria for Malignant Lymphoma (Parts A, B, and C)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with complete response (CR) or partial response (PR) through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts A, B, and C the response was assessed using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).	Up to 81 months
ORR According to the Lugano Classification Revised Staging System for Nodal Non-Hodgkin and Hodgkin Lymphomas (Lugano Criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Part D)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Part D, the response was assessed using the Lugano Classification Revised Staging System for nodal non-Hodgkin and cHL (Lugano criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).	Up to 60 months
ORR According to Modified Lugano Criteria Per Blinded Independent Central Review (BICR) (Parts E and F)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts E and F, the response was assessed per blinded independent central review (BICR) using the modified Lugano criteria.	Up to 31 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	A treatment-emergent AE (TEAE) is defined as a newly occurring or worsening AE after the first dose of any study drug component. Treatment-related AEs are defined as treatment-emergent AEs that are determined by the investigator to be related to the treatment on study. TEAEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). The CTCAE displays Grades 1 through 5, where Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, Grade 5: Death related to AE.	Up to 122 months
Number of Participants With Laboratory Abnormalities	Laboratory values were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). The CTCAE displays Grades 1 through 5, where Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, Grade 5: Death related to AE.	Up to 30 months
Complete Response Rate	Complete response rate is defined as the percentage of patients with CR	Up to 81 months
Duration of Complete Response	Duration of CR per investigator was defined as the time from start of the first documentation of CR to the first documentation of tumor progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.	Up to 81 months
Duration of Objective Response	Duration of response per investigator was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (PD) based on radiographic evidence of progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.	Up to 81 months
Progression-free Survival	Progression-free survival (PFS) per investigator was defined as the time from start of study treatment to first documentation of tumor progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.	Up to 83 months
Disease Control Rate	Disease control rate (DCR) per investigator was defined as the percentage of subjects with CR, PR, or SD, per investigator assessment of best clinical response per Cheson 2007. For Parts E and F, the assessment was per BICR.	Up to 81 months
ORR According to Lugano Criteria Per BICR (Parts E and F)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment.	Up to 31 months
B Symptom Resolution Rate	B symptom resolution rate per investigator was defined as the percentage of subjects with lymphoma-related B symptoms at baseline who achieved resolution of all B symptoms at any time during the treatment period.	Up to 42 weeks
Number of Participants With Brentuximab Vedotin Antitherapeutic Antibodies (ATA)		Up to 30 months
Number of Participants With Nivolumab Antitherapeutic Antibodies (ATA) (Part D Only)		Up to 30 months
Overall Survival (Parts E and F Only)	Overall survival (OS) per investigator was defined as the time from date of enrollment to date of death due to any cause.	Up to 44 months

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Robert Sims, MD, Seagen Inc.

Publications and helpful links

General Publications

• Friedberg JW, Forero-Torres A, Bordoni RE, Cline VJM, Patel Donnelly D, Flynn PJ, Olsen G, Chen R, Fong A, Wang Y, Yasenchak CA. Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged >/=60 years with HL. Blood. 2017 Dec 28;130(26):2829-2837. doi: 10.1182/blood-2017-06-787200. Epub 2017 Oct 16.
• Forero-Torres A, Holkova B, Goldschmidt J, Chen R, Olsen G, Boccia RV, Bordoni RE, Friedberg JW, Sharman JP, Palanca-Wessels MC, Wang Y, Yasenchak CA. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015 Dec 24;126(26):2798-804. doi: 10.1182/blood-2015-06-644336. Epub 2015 Sep 16.
• Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, Matous JV, Shustov AR, Smith SE, Zain J, O'Meara MM, Fanale MA. Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma. 2014 Oct;55(10):2328-34. doi: 10.3109/10428194.2013.876496. Epub 2014 Feb 24.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2012
• Primary Completion (Actual): April 7, 2023
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 25, 2012
• First Posted (Estimated): October 30, 2012

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy; Lymphoma; PTCL; Hematologic Diseases; Antibody-Drug Conjugate; Seattle Genetics; Antibodies, Monoclonal; Antigens, CD30; Hodgkin Disease; monomethylauristatin E; CD30-expression
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hodgkin Disease; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Immunoconjugates; Immunotoxins; Nivolumab; Bendamustine Hydrochloride; Dacarbazine; Brentuximab Vedotin
• Other Study ID Numbers: SGN35-015