Brentuximab Vedotin Plus AD in Non-bulky Limited Stage Hodgkin Lymphoma

Study Overview
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Brief Summary
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Limited stage Hodgkin lymphoma is a highly curable disease, but standard treatment with ABVD chemotherapy and radiation can lead to late risks of secondary cancers, lung injury, heart injury, and others. This trial eliminates radiation therapy and reduces intensity of chemotherapy by incorporating the highly active FDA-approved targeted therapy brentuximab vedotin, an antibody-drug conjugate specifically against the lymphoma cells, combined with the standard chemotherapy drugs Adriamycin and Dacarbazine (AD).

Detailed Description
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This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. Investigational means that the intervention is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved brentuximab vedotin (brentuximab) as part of the initial treatment of Hodgkin lymphoma. Currently, brentuximab is FDA-approved for treatment of relapsed Hodgkin lymphoma. Brentuximab works by binding specifically to Hodgkin lymphoma cells, entering the cells, and then releasing the drug to destroy the cell. The chemotherapy drugs Adriamycin and Dacarbazine (AD) which which participants will receive in this research study are approved for use in people with Hodgkin Lymphoma. Patients will not receive planned radiation therapy, or the drugs bleomycin or vinblastine.

Official Title
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Brentuximab Vedotin Plus AD 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
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated stage IA, IB, or IIA classical Hodgkin Lymphoma Non-bulky disease defined as less than 10 cm in maximal diameter Measurable disease ≥1.5 cm Age ≥18 ECOG performance status 0-2 (see Appendix B) Participants must have initial organ and marrow function as defined below: Absolute neutrophil count ≥ 1,000/mcL Platelets ≥100,000/mcL Total bilirubin ≤ 2, unless due to Gilbert's disease AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal Creatinine clearance ≥ 30 mL/min LVEF by echocardiogram or MUGA within institutional normal limits Participant must be willing to use two effective forms of birth control during protocol therapy. Men and women must continue using two effective forms of birth control for 6 months following treatment. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Participants who have had prior cHL-directed chemotherapy or radiotherapy Participants may not be receiving any other investigational agents Participants with known CNS involvement of lymphoma History of allergic reactions attributed to compounds of similar chemical or biologic composition to Adriamycin, Dacarbazine, or brentuximab Pre-existing grade 2 or greater neuropathy Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because brentuximab is an antibody drug conjugate with a linked potent anti-tubule agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with brentuximab, breastfeeding should be discontinued if the mother is treated with brentuximab. These potential risks may also apply to other agents used in this study. Participants with a history of a different malignancy are ineligible unless they have been disease free for 1 year and considered at low risk for relapse, except for: cervical cancer in situ, ductal carcinoma in situ, localized prostate cancer with no detectable disease by imaging studies, and non-melanoma cancers of the skin, which are eligible at any time. Known HIV positivity

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<br>The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle | Drug: Brentuximab Vedotin<br> <br> * Other names: Adcetris;Drug: Adriamycin<br> <br> * Other names: Rubex ®;Drug: Dacarbazine<br> <br> * Other names: Imidazole Carboxamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | The number of patients that achieved a complete response (CR) to therapy as assessed by the revised International Working Group Criteria. Complete response: Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale Bone Marrow: No evidence of FDG-avi disease No new lesions Deauville Criteria for PET scan Interpretation in Lymphoma Five-point scale: No Uptake Uptake ≤ mediastinum Uptake >mediastinum but ≤ liver Uptake moderately increased compared to liver at any site Uptake markedly increased compared to the liver at any site or/and new sites of disease | 4-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | The number of patients that achieved a complete Metabolic Response (CR) or Partial Metabolic Response (PR) to therapy as assessed by the revised International Working Group Criteria. Complete Metabolic Response: Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale Bone Marrow: No evidence of FDG-avi disease No new lesions Partial Metabolic Response: >Lymph nodes and extralymphatic sites: Score 4, 5 with reduced uptake compared with baseline and residual mass(es) of any size. Deauville Criteria for PET scan Interpretation in Lymphoma Five-point scale: No Uptake Uptake ≤ mediastinum Uptake >mediastinum but ≤ liver Uptake moderately increased compared to liver at any site Uptake markedly increased compared to the liver at any site or/and new sites of disease | 4-6 months | 
| Number of Patients With Grade III and IV Adverse Events | The number of patients that experienced grade III and grade IV adverse events that were deemed to be possibly, probably, or definitely related to study treatment. Adverse events were assessed using Common Toxicology Criteria for Adverse Events (CTCAE v4.0) criteria. | 4-6 months | 

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