Avastin (Bevacizumab) Plus Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) for Advanced Stage Hodgkin Lymphoma

Phase 2

Terminated

Conditions: Hodgkin Lymphoma

Interventions: Drug: Avastin

Registration Number: NCT00722865

Lead Sponsor: Massachusetts General Hospital

Brief Summary: The purpose of this research study is to determine the effectiveness and safety of Avastin when combined with standard chemotherapy for Hodgkin lymphoma. Avastin works differently than standard chemotherapy drugs. It is a type of protein called an antibody which binds to a substance called VEGF(Vascular Endothelial Growth Factor). VEGF stimulates the growth of the blood vessels that feed tumors and encourages tumor cell growth. VEGF is produced in excess by Hodgkin lymphoma cells, and is associated with a poorer outcome in patients with Hodgkin lymphoma. When the activity of VEGF is interrupted in multiple other cancer types, the blood vessels around the tumor cells die resulting in less nutrient delivery and death to the tumor. Blocking of VEGF has also been shown to improve delivery of chemotherapy to cancer cells, making standard chemotherapy work better. This trial uses Avastin in combination with standard chemotherapy with the goal of improving the cure rate over chemotherapy alone.

Detailed Description: Participants will be given Avastin as well as ABVD (Adriamycin, Bleomycin, Vinblastine and Dacarbazine) intravenously on days 1 and 15 of a 28 day cycle. Participants will receive up to a total of 6 cycles of therapy.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 25

Inclusion Criteria

18 years of age or older
Biopsy proven classical Hodgkin lymphoma. Classical Hodgkin lymphoma includes the subtypes of nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, and classical Hodgkin lymphoma unspecified
Advanced stage (Stage III or IV) disease
Measurable disease on cross sectional imaging
ECOG Performance Status 0-2
Adequate blood counts and organ function

Exclusion Criteria

Pregnant or lactating women
Laboratory Parameters as outlined in the protocol
LV ejection fraction lower than normal as assessed by echocardiogram or MUGA scan
DLCO less than 60% as measured by pulmonary function tests
Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for over one year
Current or recent (within 4 weeks of the first infusion of this study) participation in an experimental drug study
Life expectancy of less than 12 weeks
Inability to comply with study procedures
Inability to give informed consent
Inadequately controlled hypertension
Any prior history of hypertensive crisis or hypertensive encephalopathy
NYHA Grade II or greater congestive heart failure
History of myocardial infarction or unstable angina within 6 months prior to study enrollment
History of stroke or transient ischemic attack within 6 months prior to study enrollment
Known CNS involvement of Hodgkin lymphoma
Significant vascular disease
Symptomatic peripheral vascular disease
Evidence of bleeding diatheses or coagulopathy
Use of daily anticoagulant medications including warfarin, heparins, or aspirin >325mg daily
Major surgical procedure or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days of study enrollment
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
Serious, non-healing wound, ulcer, or bone fracture
Proteinuria at screening
Known hypersensitivity to any component of bevacizumab
Pregnant or lactating

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Avastin (Bevacizumab)	Avastin	single-arm, open-label

Primary Outcome Measures

Name	Time	Method
Failure-free Survival	2 years and median follow-up of 18 months	Failure-free survival: the absence of relapse, non-relapse mortality or addition of another systemic therapy

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate Using the Modified Cheson Criteria	2 years	Overall response = Complete response (CR) + Partial response (PR) CR = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (\<=1.5cm in greatest diameter) PR = \>=50% decrease in SPD of up to six largest dominant masses, no increase in size of other nodes; FDG avid or PET positive before therapy, one or more nodes PET positive at previously involved site, or variably FDG avid or PET negative with regression at CT
Safety	2 years	Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)
Progression-free Survival	2 years and medium follow-up of 18 months	Progression-free survival: a patient lives with the disease but it does not get worse.
Overall Survival	2 years	Overall survival: patients are still alive.