Phase 2 Study of Rituximab-ABVD in Classical Hodgkin Lymphoma

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00369681
• Other study ID #: J0615
• Secondary ID: P30CA006973NA_00
• Status: Completed
• Phase: Phase 2
• Start date: May 2006
• Est. completion date: October 2014

Study information

• Verified date: July 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Drug:
• Bleomycin

Biological:
• Rituximab

Drug:
• Dacarbazine

• Doxorubicin

• Vinblastine

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Mayo Clinic Cancer Center	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kasamon YL, Jacene HA, Gocke CD, Swinnen LJ, Gladstone DE, Perkins B, Link BK, Popplewell LL, Habermann TM, Herman JM, Matsui WH, Jones RJ, Ambinder RF. Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4129-32. doi: 10.1182/blood-2012-01-402792. Epub 2012 Feb 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of Rituximab on EBV(+) Tumors	Number of relapses among participants who had tumors positive for Epstein-Barr virus (EBV).	Up to 56 months
Primary	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	Event-free Survival	Percentage of participants who did not experience death, relapse, or progression (worsening) of their lymphoma.	3 years
Secondary	Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers		5 years