A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for CD30-Positive Mature T-Cell and NK-Cell Neoplasms

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety profile of brentuximab vedotin sequentially and in combination with multi-agent chemotherapy in front-line treatment for CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma. It is a phase 1, open-label, dose escalation study in three arms designed to define the MTD, PK, immunogenicity, and anti-tumor activity of brentuximab vedotin in sequence and in combination with multi-agent front-line chemotherapy.

Official Title
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A Phase 1 Study of Brentuximab Vedotin Administered Sequentially and Concurrently With Multi-Agent Chemotherapy as Front-Line Therapy in Patients With CD30-Positive Mature T-Cell and NK-Cell Neoplasms, Including Systemic Anaplastic Large Cell Lymphoma

Conditions
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Lymphoma, Large-Cell, Anaplastic, Lymphoma, NK-cell, Lymphoma, T-cell

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: cyclophosphamide
* Drug: brentuximab vedotin
* Drug: prednisone
* Drug: cyclophosphamide
* Drug: doxorubicin
* Drug: doxorubicin
* Drug: prednisone
* Drug: vincristine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment-naive CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma Measurable disease of at least 1.5 cm ECOG performance status less than or equal to 2 Exclusion Criteria: Known cerebral/meningeal disease, including history of progressive multifocal leukoencephalopathy Current diagnosis of primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, Sezary syndrome or other primary cutaneous lymphomas; extranodal NK/T-cell lymphoma, nasal type History of another primary malignancy that has not been in remission for at least 3 years Left ventricular ejection fraction <45% or symptomatic cardiac disease, or myocardial infarction within the past 12 months Viral, bacterial, or fungal infection within two weeks prior to the first dose of brentuximab vedotin Known human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus positive status

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Sequential | Drug: brentuximab vedotin<br>* 1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-2 and if response, Cycles 9-16)<br>* Other names: SGN-35;Drug: cyclophosphamide<br>* 750 mg/m2 IV every 3 weeks (Cycles 3-8)<br>Drug: prednisone<br>* 100 mg daily PO on Days 1-5 every 3 weeks (Cycles 3-8)<br>Drug: doxorubicin<br>* 50 mg/m2 IV every 3 weeks (Cycles 3-8)<br>Drug: vincristine<br>* 1.4 mg/m2 IV every 3 weeks (Cycles 3-8)<br>|
| Experimental: 2<br>Combination | Drug: brentuximab vedotin<br>* 1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-6 and if response, Cycles 7-16)<br>* Other names: SGN-35;Drug: cyclophosphamide<br>* 750 mg/m2 IV every 3 weeks (Cycles 1-6)<br>Drug: doxorubicin<br>* 50 mg/m2 IV every 3 weeks (Cycles 1-6)<br>Drug: prednisone<br>* 100 mg daily PO on Days 1-5 every 3 weeks (Cycles 1-6)<br>|
| Experimental: 3 Brentuximab vedotin/CH-P<br>Combination | Drug: brentuximab vedotin<br>* 1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-6 and if response, Cycles 7-16)<br>* Other names: SGN-35;Drug: cyclophosphamide<br>* 750 mg/m2 IV every 3 weeks (Cycles 1-6)<br>Drug: doxorubicin<br>* 50 mg/m2 IV every 3 weeks (Cycles 1-6)<br>Drug: prednisone<br>* 100 mg daily PO on Days 1-5 every 3 weeks (Cycles 1-6)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and laboratory abnormalities |  | Through 1 month after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brentuximab vedotin concentration in blood |  | Through 1 month after last dose | 
| Antitherapeutic antibodies in blood |  | Through 1 month after last dose | 
| Best clinical response |  | Through 1 month after last dose | 
| Progression-free survival |  | Until disease progression or study closure | 
| Overall survival |  | Every 3 months until death or study closure | 

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