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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
176
1.8 mg/kg every 3 weeks by IV infusion
375 mg/m2 every 3 weeks by IV infusion
University of Alabama at Birmingham
Birmingham, Alabama, United States
City of Hope
Duarte, California, United States
PMK Medical Group Inc., DBA Ventura County Hematology Oncology Specialists
Oxnard, California, United States
Stanford Cancer Center
Stanford, California, United States
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado, United States
Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy
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.
Time frame: Up to approximately 3 years
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab
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.
Time frame: Up to 3 years
Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab
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.
Time frame: Up to approximately 3 years
Complete Remission (CR) Rate by Investigator
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.
Time frame: Up to approximately 3 years
Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
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.
Time frame: Up to approximately 3 years
Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
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.
Time frame: Up to approximately 3 years
Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
Time frame: Up to approximately 3 years
Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression
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).
Time frame: Up to 3 years
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy
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.
Time frame: Up to 3 years
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1)
End of infusion concentration of ADC following the first dose of brentuximab vedotin
Time frame: 1 day
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1)
Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1)
Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Baseline Soluble CD30 Expression
Serum concentration of soluble CD30 before first dose of brentuximab vedotin
Time frame: Baseline
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Colorado Blood Cancer Institute
Denver, Colorado, United States
Cancer Specialists of North Florida - St. Augustine
Saint Augustine, Florida, United States
Emory Winship Cancer Institute
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
...and 24 more locations