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Phase 2 Study of Rituximab-ABVD in Classical Hodgkin Lymphoma

Phase 2
Completed
Conditions
Lymphoma
Interventions
Registration Number
NCT00369681
Lead Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
51
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
R-ABVDBleomycinABVD (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.
R-ABVDRituximabABVD (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.
R-ABVDDacarbazineABVD (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.
R-ABVDDoxorubicinABVD (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.
R-ABVDVinblastineABVD (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.
Primary Outcome Measures
NameTimeMethod
Relationship Between Marker Detection and Clinical Outcome3 years

Number of relapses for participants who did and did not have re-emergence of clonal CD27(+) ALDH(+) B cells after completing study intervention.

Effect of Rituximab on EBV(+) TumorsUp to 56 months

Number of relapses among participants who had tumors positive for Epstein-Barr virus (EBV).

Secondary Outcome Measures
NameTimeMethod
Event-free Survival3 years

Percentage of participants who did not experience death, relapse, or progression (worsening) of their lymphoma.

Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers5 years

Trial Locations

Locations (4)

City of Hope Comprehensive Cancer Center

🇺🇸

Duarte, California, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

Holden Comprehensive Cancer Center at University of Iowa

🇺🇸

Iowa City, Iowa, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

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