Phase 2 Study of Rituximab-ABVD in Classical Hodgkin Lymphoma

Johns Hopkins Medicine

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: Bleomycin; Drug: Doxorubicin; Biological: Rituximab; Drug: Dacarbazine; Drug: Vinblastine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00369681

P30CA006973 (U.S. NIH Grant/Contract)

NA_00002473 (Other Identifier)

J0615

Details and patient eligibility

About

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.

Full 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.

Enrollment: 51 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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51 participants in 1 patient group

R-ABVD

Experimental group

Description:

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.

Treatment:

Drug: Vinblastine

Drug: Dacarbazine

Biological: Rituximab

Drug: Doxorubicin

Drug: Bleomycin