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

Phase 2
Completed
Conditions
Hodgkin Disease
Peripheral T Cell Lymphoma
Interventions
Registration Number
NCT01716806
Lead Sponsor
Seagen Inc.
Brief Summary

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.

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
131
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part C: Brentuximab Vedotin + Bendamustine in HL Patientsbrentuximab vedotin-
Part C: Brentuximab Vedotin + Bendamustine in HL Patientsbendamustine-
Part D: Brentuximab Vedotin + Nivolumab in HL Patientsbrentuximab vedotin-
Part F: Brentuximab Vedotin in PTCL Patientsbrentuximab vedotin-
Part B: Brentuximab Vedotin + Dacarbazine in HL Patientsdacarbazine-
Part B: Brentuximab Vedotin + Dacarbazine in HL Patientsbrentuximab vedotin-
Part A: Brentuximab Vedotin in HL Patientsbrentuximab vedotin-
Part D: Brentuximab Vedotin + Nivolumab in HL Patientsnivolumab-
Part E: Brentuximab Vedotin in HL Patientsbrentuximab vedotin-
Primary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) According to the Revised Response Criteria for Malignant Lymphoma (Parts A, B, and C)Up to 81 months

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).

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)Up to 60 months

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).

ORR According to Modified Lugano Criteria Per Blinded Independent Central Review (BICR) (Parts E and F)Up to 31 months

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.

Secondary Outcome Measures
NameTimeMethod
Disease Control RateUp to 81 months

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.

ORR According to Lugano Criteria Per BICR (Parts E and F)Up to 31 months

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.

Number of Participants With Adverse EventsUp to 122 months

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.

Number of Participants With Laboratory AbnormalitiesUp to 30 months

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.

Complete Response RateUp to 81 months

Complete response rate is defined as the percentage of patients with CR

Duration of Complete ResponseUp to 81 months

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.

Duration of Objective ResponseUp to 81 months

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.

Progression-free SurvivalUp to 83 months

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.

B Symptom Resolution RateUp to 42 weeks

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.

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)Up to 44 months

Overall survival (OS) per investigator was defined as the time from date of enrollment to date of death due to any cause.

Trial Locations

Locations (54)

Wenatchee Valley Medical Center

🇺🇸

Wenatchee, Washington, United States

James Cancer Hospital / Ohio State University

🇺🇸

Columbus, Ohio, United States

Swedish Cancer Institute

🇺🇸

Seattle, Washington, United States

MD Anderson Cancer Center / University of Texas

🇺🇸

Houston, Texas, United States

Oncology Hematology Care

🇺🇸

Cincinnati, Ohio, United States

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

Rutgers Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

Nebraska Cancer Specialists

🇺🇸

Omaha, Nebraska, United States

Banner MD Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Rocky Mountain Cancer Centers - Aurora

🇺🇸

Aurora, Colorado, United States

Morristown Medical Center/ Carol G. Simon Cancer Center

🇺🇸

Morristown, New Jersey, United States

Houston Methodist Cancer Center

🇺🇸

Houston, Texas, United States

Virginia Cancer Specialists, PC

🇺🇸

Fairfax, Virginia, United States

American Oncology Networks LLC

🇺🇸

Bethesda, Maryland, United States

Wilshire Oncology Medical Group Inc.

🇺🇸

Pomona, California, United States

University of Alberta / Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Texas Oncology - Denton South

🇺🇸

Denton, Texas, United States

Providence St Joseph Medical Center

🇺🇸

Burbank, California, United States

Georgia Cancer Specialists / Northside Hospital Cancer Institute

🇺🇸

Sandy Springs, Georgia, United States

CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

Arlington Cancer Center

🇺🇸

Arlington, Texas, United States

Florida Cancer Affiliates

🇺🇸

Trinity, Florida, United States

Karmanos Cancer Institute / Wayne State University

🇺🇸

Detroit, Michigan, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Virginia Commonwealth University Medical Center

🇺🇸

Richmond, Virginia, United States

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

University of South Alabama - Mitchell Cancer Institute

🇺🇸

Mobile, Alabama, United States

Highlands Oncology Group

🇺🇸

Springdale, Arkansas, United States

London Health Sciences Centre - Victoria Hospital

🇨🇦

London, Ontario, Canada

Arizona Cancer Center / University of Arizona

🇺🇸

Tucson, Arizona, United States

Texas Oncology - Seton Williamson

🇺🇸

Round Rock, Texas, United States

Comprehensive Cancer Centers of Nevada

🇺🇸

Las Vegas, Nevada, United States

Shenandoah Oncology P.C.

🇺🇸

Winchester, Virginia, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Alaska Urological Institute

🇺🇸

Anchorage, Alaska, United States

IACT Health

🇺🇸

Columbus, Georgia, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Illinois Cancer Specialists / Advocate Lutheran General Hospital

🇺🇸

Niles, Illinois, United States

Northwest Cancer Specialists, P.C.

🇺🇸

Tigard, Oregon, United States

New York Oncology Hematology, P.C.

🇺🇸

Albany, New York, United States

Minnesota Oncology Hematology P.A.

🇺🇸

Minneapolis, Minnesota, United States

James P. Wilmot Cancer Center / University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Texas Oncology - Bedford

🇺🇸

Bedford, Texas, United States

Texas Oncology - Fort Worth 12th Avenue

🇺🇸

Fort Worth, Texas, United States

Texas Oncology - Longview

🇺🇸

Longview, Texas, United States

Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care

🇺🇸

Salem, Virginia, United States

Carbone Cancer Center / University of Wisconsin

🇺🇸

Madison, Wisconsin, United States

Benaroya Research Institute/Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

Royal Victoria Hospital, McGill University Health Centre

🇨🇦

Montreal, Quebec, Canada

Willamette Valley Cancer Institute and Research Center

🇺🇸

Eugene, Oregon, United States

Arizona Oncology Associates, PC - HOPE

🇺🇸

Tucson, Arizona, United States

Prisma Health

🇺🇸

Greenville, South Carolina, United States

Texas Oncology - McAllen

🇺🇸

McAllen, Texas, United States

Texas Oncology - Presbyterian Cancer Center Dallas

🇺🇸

Dallas, Texas, United States

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