Phase 2 Study of Rituximab-ABVD in Classical Hodgkin Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with newly diagnosed stage II, stage III, or stage IV Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Investigate plasma DNA biomarkers, including plasma clonal immunoglobulin DNA, tumor suppressor gene methylation, and Epstein-Barr virus DNA, in patients receiving rituximab and doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD) for newly diagnosed stage II-IV classical Hodgkin's lymphoma. Characterize the impact of rituximab on these markers. Characterize the relationship between marker detection and clinical outcome. Secondary Estimate the event-free survival of patients with newly diagnosed Hodgkin's lymphoma treated with rituximab and ABVD. Assess the presence of Hodgkin's lymphoma stem cells in peripheral blood mononuclear cells at baseline, after treatment with rituximab, and after treatment with ABVD. Assess whether plasma DNA biomarkers add information to fludeoxyglucose F 18 positron emission tomography (FDG-PET) in assessing tumor response. OUTLINE: Patients receive doxorubicin hydrochloride IV, vinblastine IV, bleomycin IV, and dacarbazine IV (ABVD) on days 1 and 15 of all courses. Patients also receive rituximab IV on days -6, 1, 8, 15, and 22 of ABVD course 1 and on day 1 only of ABVD courses 2, 4, and 6. Treatment repeats every 28 days for 6-8 courses in the absence of disease progression or unacceptable toxicity. Patients with bulky disease may undergo radiotherapy. Plasma samples are obtained during treatment for investigation of tumor markers (e.g., immunoglobulin rearrangement, patterns of DNA methylation, and the presence of Epstein-Barr virus DNA). Patients undergo fludeoxyglucose F18 positron emission tomography periodically during the study. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Bleomycin
* Biological: Rituximab
* Drug: Dacarbazine
* Drug: Doxorubicin
* Drug: Vinblastine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed classical Hodgkin's lymphoma No lymphocyte-predominant histology Stage II, III, or IV disease Newly diagnosed disease PATIENT CHARACTERISTICS: Performance status 0-2 Creatinine < 2.0 mg/dL Bilirubin < 5 mg/dL Not pregnant or nursing No HIV positivity Hepatitis B surface antigen negative No active concurrent malignancy except for superficial nonmelanoma skin cancer or cervical carcinoma in situ PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for Hodgkin's lymphoma Steroids allowed if medically required before chemotherapy initiation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: R-ABVD<br>ABVD (doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1. | Drug: Bleomycin<br> <br> * Other names: Blenoxane;Biological: Rituximab<br> <br> * Other names: Rituxan;Drug: Dacarbazine<br> <br> * Other names: DTIC-Dome;Drug: Doxorubicin<br> <br> * Other names: Adriamycin;Drug: Vinblastine<br> <br> * Other names: Alkaban;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Rituximab on EBV(+) Tumors | Number of relapses among participants who had tumors positive for Epstein-Barr virus (EBV). | Up to 56 months | 
| Relationship Between Marker Detection and Clinical Outcome | Number of relapses for participants who did and did not have re-emergence of clonal CD27(+) ALDH(+) B cells after completing study intervention. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival | Percentage of participants who did not experience death, relapse, or progression (worsening) of their lymphoma. | 3 years | 
| Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, adult lymphocyte depletion Hodgkin lymphoma, adult mixed cellularity Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma