Study of Brentuximab Vedotin Combined With Bendamustine in Patients With Hodgkin Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to assess safety and efficacy of brentuximab vedotin in combination with bendamustine in patients with relapsed or refractory Hodgkin lymphoma. It is an open-label, 2-stage study designed to determine the recommended dose level of bendamustine in combination with brentuximab vedotin. The study will assess the safety profile of the combination treatment and determine what proportion of patients achieve a complete remission.

Official Title
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A Phase 1/2 Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Brentuximab Vedotin in Combination With Bendamustine in Patients With Relapsed or Refractory Hodgkin Lymphoma (HL)

Conditions
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Hodgkin Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathological diagnosis of classical Hodgkin lymphoma Failed standard front-line therapy Measurable disease of at least 1.5 cm as documented by radiographic technique Eastern Cooperative Oncology Group performance status less than or equal to 2 Exclusion Criteria: Received prior salvage therapy, including radiotherapy Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy not completed 4 weeks prior to first dose of study drug Concurrent use of other investigational agents

Ages Eligible for Study
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Minimum Age: 18 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 + Bendamustine<br>Brentuximab vedotin 1.8 mg/kg every 3 weeks for up to 16 cycles by IV infusion and bendamustine 90 mg/m2 on Days 1 and 2 every 3 weeks by IV infusion for up to 6 cycles | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by intravenous (IV) infusion<br>* Other names: Adcetris; SGN-35;Drug: bendamustine<br>* 90 mg/m2 on Days 1 and 2 of 3-week cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate | Complete remission rate among all subjects (Phase 1 and 2 combined) treated at the dose level selected for Phase 2. Complete remission (CR) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma is a disappearance of all evidence of disease. | Up to 4.6 months | 
| Incidence of Adverse Events (AEs) | All AEs reported after initiation of treatment and pre-existing conditions that worsen after initiation of treatment will be considered treatment-emergent AEs (TEAEs). All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE V4.03. All recorded AEs will be included in the data listings. | Up to 13.8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose-limiting Toxicities | Incidence of dose-limiting toxicity (DLT) was evaluated in an initial safety cohort of 10 patients who were followed for protocol-defined DLT events until Cycle 2 Day 1. | Up to 3 weeks; first cycle of therapy through the first day of Cycle 2 | 
| Overall Best Response Rate | Percentage of participants 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), stable disease (SD, failure to obtain a complete or partial response or progressive disease), or progressive disease (PD, any new lesion or increase by 50% or more of previously involved sites from nadir) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma | Up to 4.6 months | 
| Duration of Response | The time from first observation of remission to disease progression/relapse or death from any cause, whichever occurs first. | Up to 47.8 months | 
| Progression-free Survival | The time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first. | Up to 49 months | 

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