A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 2 Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma (NHL)

Conditions
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Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab vedotin+rituximab<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;Drug: rituximab<br>* 375 mg/m2 every 3 weeks by IV infusion<br>|
| Experimental: Brentuximab vedotin<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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 | 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). | 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. | 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 | 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 | 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 | 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 | 3 weeks | 
| Baseline Soluble CD30 Expression | Serum concentration of soluble CD30 before first dose of brentuximab vedotin | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Large B-Cell, Diffuse, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Lymphoma, Lymphoma, B-Cell, Lymphoma, T-Cell