Brentuximab Vedotin Plus AVD in Limited-stage Hodgkin Lymphoma

Study Overview
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Brief Summary
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Brentuximab is an antibody-drug conjugate (ADC), which is the combination of an antibody (a protein that binds to cells) and a chemotherapy molecule. Brentuximab works by using the antibody portion to enter into the Hodgkin lymphoma cells and then releasing the chemotherapy portion, which attempts to destroy the cell. The intravenous chemotherapy drugs Adriamycin, Vinblastine and Dacarbazine (AVD) which you will receive in this research study are approved for use in people with Hodgkin Lymphoma. A drug called bleomycin is usually included with AVD, but since it appears to be a less effective drug with significant potential risks, it is being replaced in this study with the drug brentuximab. In this research study, the investigators are looking to see whether brentuximab in combination with AVD is effective in treating limited-stage Hodgkin Lymphoma.

Detailed Description
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Each treatment cycle is 28 days. You will receive brentuximab alone on Day 1 and 15 of the first cycle (lead-in cycle). After cycle 1, you will receive brentuximab combined with AVD on Day 1 and 15 for 4-6 cycles, depending on your response to therapy. Brentuximab and AVD will be given to you by intravenous infusion (IV). The following test and procedures will be performed on Days 1 and 15 of each cycle: Review of any side effects you have experienced and all medications you are taking Performance Status Physical exam and vital signs Routine blood tests Questionnaire to evaluate symptoms of neuropathy Research blood sample to look at markers to see how your body is responding to study medication PET-CT scan prior to completing cycle 2 of combination brentuximab/AVD After the final dose of the study drug: The following assessments will be performed within one month of your last dose of study medication: Review of any side effects you have experienced and all medications you are taking Performance Status Physical exam and vital signs Routine blood tests Questionnaire to evaluate symptoms of neuropathy Research blood sample to look at markers to see how your body is responding to study medication PET-CT scan Follow up will include the following Review of any side effects you have experienced and all medications you are taking Performance Status Review and Physical exam Routine blood tests Questionnaire to evaluate symptoms of neuropathy CT scans

Official Title
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Brentuximab Vedotin Plus AVD in Non-bulky Limited Stage Hodgkin Lymphoma

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Brentuximab Vedotin
* Drug: Adriamycin, vinblastine, and dacarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated stage IA, IB, IIA or IIB classical Hodgkin Lymphoma Non-bulky disease defined as less than 10 cm in maximal diameter Measurable disease greater than or equal to 1.5 cm ECOG performance status of 0 or 2 Willing to use 2 effective forms of birth control Exclusion Criteria: No prior chemotherapy or radiotherapy for Hodgkin lymphoma Not receiving any other investigational agents No history of allergic reactions attributed to compounds of similar chemical or biologic composition to Adriamycin, Vinblastine, Dacarbazine or brentuximab No pre-existing grade 3 or greater neuropathy No uncontrolled intercurrent illness Not pregnant or breastfeeding No history of a different malignancy unless disease free for at least one year

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: Treatment Arm<br>Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine | Drug: Brentuximab Vedotin<br>* 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg<br>* Other names: SGN35;Drug: Adriamycin, vinblastine, and dacarbazine<br>* Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine<br>* Other names: DTIC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | Complete response rate at the end of therapy as measured by Positron emission tomography-computed tomography (PET/CT). Response is evaluated using Revised International Working Group Criteria. Complete response is defined as disappearance of all evidence of disease. | End of Therapy (median duration of four months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate After One Cycle of Brentuximab | The number of participants achieving a Partial Response (PR) or Complete Response (CR) after one cycle of Brentuximab monotherapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites | 28 days | 
| Overall Response Rate | The number of participants achieving a Partial Response (PR) or Complete Response (CR) at the end of therapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites | End of Therapy (median duration of four months) | 
| Grade III or IV Adverse Events | A summary of the grade 3 or 4 adverse events experienced by participants as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The data is shown as the number of participants that experienced at least one grade 3 or 4 adverse event for each of the specified toxicities. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-bulky, limited stage