A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma

Study Overview
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Brief Summary
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This is a single-arm, open-label, multicenter, pivotal clinical trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) as a single agent in patients with relapsed or refractory Hodgkin lymphoma.

Official Title
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A Pivotal Study of SGN-35 in Treatment of Patients With Relapsed or Refractory Hodgkin Lymphoma (HL)

Conditions
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Disease, Hodgkin

Intervention / Treatment
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* Drug: brentuximab vedotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsed or refractory Hodgkin lymphoma who have previously received autologous stem cell transplant. Histologically confirmed CD30-positive disease; tissue from the most recent post diagnostic biopsy of relapsed/refractory disease must be available for confirmation of CD30 expression via slides or tumor block. Fluorodeoxyglucose-avid disease by positron emission tomography and measurable disease of at least 1.5 cm as documented by spiral computed tomography. At US sites patients greater than or equal to 12 years of age may be enrolled. At non-US sites patients must be greater than or equal to 18 years of age. Exclusion Criteria: Previous treatment with brentuximab vedotin. Previously received an allogeneic transplant. Congestive heart failure, Class III or IV, by the New York Heart Association criteria. History of another primary malignancy that has not been in remission for at least 3 years. Known cerebral/meningeal disease.

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab vedotin<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by intravenous infusion<br>* Other names: ADCETRIS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate by Independent Review Group | Percentage of participants 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 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate by Independent Review Group | Percentage of participants who achieved a best response of CR (disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. | up to 12 months | 
| Duration of Objective Response by Kaplan-Meier Analysis | Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death. | up to approximately 4 years | 
| Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis | Duration of response from start of first objective tumor response (CR or PR) by independent review group to disease progression or death due to any cause in participants with CR. | up to approximately 4 years | 
| Progression-free Survival by Kaplan-Meier Analysis | Time from start of study treatment to disease progression per independent review group or death due to any cause. | up to approximately 4 years | 
| Overall Survival | Time from start of study treatment to date of death due to any cause. | up to approximately 6 years | 
| Adverse Events by Severity, Seriousness, and Relationship to Treatment | Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). 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 12 months | 
| Hematology Laboratory Abnormalities >/= Grade 3 | Counts of study participants with post-baseline hematology laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category. | up to 12 months | 
| Chemistry Laboratory Abnormalities >/= Grade 3 | Counts of study participants with post-baseline chemistry laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category. | up to 12 months | 
| Area Under the Curve | Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin | 3 weeks | 
| Maximum Serum Concentration | Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin | 3 weeks | 
| Time of Maximum Serum Concentration | Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Disease, Hodgkin, Hematologic Diseases, Lymphoma, monomethylauristatin E, Drug Therapy, Immunotherapy