Clinical Pharmacology Study of Brentuximab Vedotin (SGN-35)

Study Overview
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Brief Summary
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The purpose of this study is to identify brentuximab vedotin drug-drug interactions in patients with CD30-positive cancers and to determine the main route of excretion. The study will also assess blood drug levels in patients with renal or hepatic impairment (special populations).

Official Title
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An Open-Label Clinical Pharmacology Study of Brentuximab Vedotin (SGN-35) in Patients With CD30-Positive Hematologic Malignancies: CYP3A4 Drug-Drug Interactions, Excretion, and Special Populations

Conditions
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Carcinomas, Disease, Hodgkin, Lymphoma, Large-Cell, Anaplastic, Lymphoma, Non-Hodgkin, Neoplasms

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: rifampin
* Drug: midazolam
* Drug: ketoconazole
* Drug: brentuximab vedotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adequate organ function (Special Populations: serum bilirubin >2 mg/dL or creatinine clearance <50 mL/min) ECOG performance status <2 (Special Populations: <4) Relapsed or refractory CD30-positive malignancy Exclusion Criteria: Receiving prohibited medication within 4 weeks Poor liver function (Child-Pugh class C) Current diagnosis of primary cutaneous ALCL Acute or chronic graft-versus-host disease

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>midazolam +/- brentuximab vedotin | Drug: brentuximab vedotin<br>* 1.8 mg/kg IV every 21 days<br>* Other names: ADCETRIS; SGN-35;Drug: midazolam<br>* 1 mg IV<br>|
| Experimental: 2<br>brentuximab vedotin +/- rifampin | Drug: brentuximab vedotin<br>* 1.8 mg/kg IV every 21 days<br>* Other names: ADCETRIS; SGN-35;Drug: rifampin<br>* 600 mg/day PO<br>|
| Experimental: 3<br>brentuximab vedotin +/- ketoconazole | Drug: ketoconazole<br>* 400 mg/day PO<br>Drug: brentuximab vedotin<br>* 1.2 mg/kg IV every 21 days<br>* Other names: SGN-35;|
| Experimental: 4<br>special populations | Drug: brentuximab vedotin<br>* 1.2 mg/kg IV every 21 days<br>* Other names: SGN-35;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midazolam blood concentrations +/- brentuximab vedotin |  | 3 weeks | 
| Brentuximab vedotin blood concentrations +/- rifampin |  | 6 weeks | 
| Brentuximab vedotin in urine, feces, and blood |  | 1 week | 
| Brentuximab vedotin blood concentrations in special populations |  | 3 weeks | 
| Brentuximab vedotin blood concentrations +/- ketoconazole |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and laboratory abnormalities |  | 6 weeks | 

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