A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma
- Conditions
- Lymphoma, Non-HodgkinLymphoma, B-CellLymphoma, Large B-Cell, DiffuseLymphoma, T-Cell
- Interventions
- Registration Number
- NCT01421667
- Lead Sponsor
- Seagen Inc.
- Brief Summary
This is an open-label, multicenter, phase 2 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in patients with CD30-positive non-Hodgkin lymphoma (NHL) (Part A). The study will also evaluate the safety and efficacy of brentuximab vedotin in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Part B) as well as further evaluate correlation of CD30 expression and response in DLBCL (Part C).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 176
- Histologically-confirmed NHL (DLBCL only for Parts B and C)
- Relapsed or refractory disease following at least 1 prior systemic therapy
- Measurable disease of at least 1.5 cm as documented by CT
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
- History of another primary invasive malignancy that has not been in remission for at least 3 years
- Current diagnosis of systemic or cutaneous anaplastic large cell lymphoma or mycosis fungoides
- B cell lymphoma previously treated with only single-agent rituximab (for patients receiving brentuximab vedotin only) or corticosteroids as monotherapy
- Known cerebral/meningeal disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Brentuximab vedotin+rituximab brentuximab vedotin - Brentuximab vedotin+rituximab rituximab - Brentuximab vedotin brentuximab vedotin -
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy Up to approximately 3 years Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab Up to 3 years Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
- Secondary Outcome Measures
Name Time Method Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis Up to approximately 3 years Duration of complete remission (CR) or partial remission (PR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab Up to approximately 3 years Percentage of participants treated with brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Complete Remission (CR) Rate by Investigator Up to approximately 3 years Percentage of participants treated with brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis Up to approximately 3 years Duration of complete remission (CR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression Up to 3 years Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), or stable disease (SD, no new sites and no change in size of previous lesions) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Patients are grouped by CD30-positivity or CD30u (undetectable CD30).
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1) 1 day End of infusion concentration of ADC following the first dose of brentuximab vedotin
Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) 3 weeks Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis Up to approximately 3 years Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy Up to 3 years Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1) 3 weeks Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin
Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1) 3 weeks Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Baseline Soluble CD30 Expression Baseline Serum concentration of soluble CD30 before first dose of brentuximab vedotin
Trial Locations
- Locations (34)
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
British Columbia Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
City of Hope
🇺🇸Duarte, California, United States
PMK Medical Group Inc., DBA Ventura County Hematology Oncology Specialists
🇺🇸Oxnard, California, United States
Emory Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Cleveland Clinic, The
🇺🇸Cleveland, Ohio, United States
NYU Clinical Cancer Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Texas Oncology - Medical City Dallas
🇺🇸Dallas, Texas, United States
Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Texas Oncology - Seton Williamson
🇺🇸Round Rock, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Swedish Cancer Institute Medical Oncology
🇺🇸Edmonds, Washington, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Texas Oncology-Southwest Fort Worth
🇺🇸Fort Worth, Texas, United States
Northwest Cancer Specialists, P.C.
🇺🇸Vancouver, Washington, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Rocky Mountain Cancer Centers - Aurora
🇺🇸Aurora, Colorado, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Minnesota Oncology Hematology P.A.
🇺🇸Minneapolis, Minnesota, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance / University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Cancer Specialists of North Florida - St. Augustine
🇺🇸St. Augustine, Florida, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Willamette Valley Cancer and Research / USOR
🇺🇸Eugene, Oregon, United States
St. Francis Hospital
🇺🇸Greenville, South Carolina, United States