Clinical trial NCT00369681: Phase 2 Study of Rituximab-ABVD in Classical Hodgkin Lymphoma
Official title: Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-08-29
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Effect of Rituximab on EBV(+) Tumors
timeFrame: Up to 56 months
measure: Relationship Between Marker Detection and Clinical Outcome
timeFrame: 3 years
Secondary outcomes:
measure: Event-free Survival
timeFrame: 3 years
measure: Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers
timeFrame: 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Yvette L. Kasamon, MD
role: STUDY_CHAIR
References:
citation: 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.