Hodgkin Lymphoma
Conditions
Keywords
Avastin, bevacizumab, ABVD, angiogenesis, antiangiogenic, Hodgkin
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.
Interventions
DRUGAvastin
Given intravenously along with standard chemotherapy (Adriamycin, Bleomycin, Vinblastine and Dacarbazine) on days 1 and 15 of a 28-day cycle for a total of 6 planned cycles.
Sponsors
Genentech, Inc.
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| Safety | 2 years | Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Avastin (Bevacizumab) single-arm, open-label
Avastin: Given intravenously along with standard chemotherapy (Adriamycin, Bleomycin, Vinblastine and Dacarbazine) on days 1 and 15 of a 28-day cycle for a total of 6 planned cycles. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Avastin (Bevacizumab) |
|---|---|
| Absolute lymphocyte count <600/uL | 4 Participants |
| Absolute lymphocyte count >=600/uL | 21 Participants |
| Age, Continuous | 29 years |
| Albumin <4.0 g/dL | 17 Participants |
| Albumin >=4.0 g/dL | 8 Participants |
| B symptoms No | 10 Participants |
| B symptoms Yes | 15 Participants |
| Hemoglobin <10.5 g/dL | 7 Participants |
| Hemoglobin >=10.5 g/dL | 18 Participants |
| International Prognostic Scoring System (IPSS) 0 | 1 Participants |
| International Prognostic Scoring System (IPSS) 1 | 5 Participants |
| International Prognostic Scoring System (IPSS) 2 | 5 Participants |
| International Prognostic Scoring System (IPSS) 3 | 4 Participants |
| International Prognostic Scoring System (IPSS) 4 | 7 Participants |
| International Prognostic Scoring System (IPSS) 5 | 3 Participants |
| Leukocytosis <=15,000/uL | 20 Participants |
| Leukocytosis >15,000/uL | 5 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 15 Participants |
| Stage of Cancer Stage III | 10 Participants |
| Stage of Cancer Stage IV | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 4 / 25 |
Outcome results
Primary
Failure-free Survival
Failure-free survival: the absence of relapse, non-relapse mortality or addition of another systemic therapy
Time frame: 2 years and median follow-up of 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avastin (Bevacizumab) | Failure-free Survival | at 2 years | 67 percentage of participants |
| Avastin (Bevacizumab) | Failure-free Survival | at median follow-up of 18 months | 73 percentage of participants |
Secondary
Overall Response Rate Using the Modified Cheson Criteria
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
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avastin (Bevacizumab) | Overall Response Rate Using the Modified Cheson Criteria | 96 percentage of participants |
Secondary
Overall Survival
Overall survival: patients are still alive.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avastin (Bevacizumab) | Overall Survival | 25 Participants |
Secondary
Progression-free Survival
Progression-free survival: a patient lives with the disease but it does not get worse.
Time frame: 2 years and medium follow-up of 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avastin (Bevacizumab) | Progression-free Survival | at 2 years | 67 percentage of participants |
| Avastin (Bevacizumab) | Progression-free Survival | at median follow-up of 18 months | 73 percentage of participants |
Secondary
Safety
Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)
Time frame: 2 years
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Avastin (Bevacizumab) | Safety | Anemia | Grade 1-2 | 19 Participants |
| Avastin (Bevacizumab) | Safety | Anemia | Grade 3-4 | 3 Participants |
| Avastin (Bevacizumab) | Safety | Anemia | Did not have any | 3 Participants |
| Avastin (Bevacizumab) | Safety | Neutropenia | Grade 1-2 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Neutropenia | Grade 3-4 | 22 Participants |
| Avastin (Bevacizumab) | Safety | Neutropenia | Did not have any | 2 Participants |
| Avastin (Bevacizumab) | Safety | Thrombocytopenia | Grade 1-2 | 3 Participants |
| Avastin (Bevacizumab) | Safety | Thrombocytopenia | Grade 3-4 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Thrombocytopenia | Did not have any | 22 Participants |
| Avastin (Bevacizumab) | Safety | Febrile neutropenia | Grade 1-2 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Febrile neutropenia | Grade 3-4 | 4 Participants |
| Avastin (Bevacizumab) | Safety | Febrile neutropenia | Did not have any | 21 Participants |
| Avastin (Bevacizumab) | Safety | Hypertension | Grade 1-2 | 2 Participants |
| Avastin (Bevacizumab) | Safety | Hypertension | Grade 3-4 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Hypertension | Did not have any | 22 Participants |
| Avastin (Bevacizumab) | Safety | Proteinuria | Grade 1-2 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Proteinuria | Grade 3-4 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Proteinuria | Did not have any | 25 Participants |
| Avastin (Bevacizumab) | Safety | Pericardial effusion | Grade 1-2 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Pericardial effusion | Grade 3-4 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Pericardial effusion | Did not have any | 23 Participants |
| Avastin (Bevacizumab) | Safety | Pleural effusion | Grade 1-2 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Pleural effusion | Grade 3-4 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Pleural effusion | Did not have any | 24 Participants |
| Avastin (Bevacizumab) | Safety | Skin breakdown | Grade 1-2 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Skin breakdown | Grade 3-4 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Skin breakdown | Did not have any | 24 Participants |
| Avastin (Bevacizumab) | Safety | Mucositis | Grade 1-2 | 4 Participants |
| Avastin (Bevacizumab) | Safety | Mucositis | Grade 3-4 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Mucositis | Did not have any | 21 Participants |
| Avastin (Bevacizumab) | Safety | Sensory neuropathy | Grade 1-2 | 8 Participants |
| Avastin (Bevacizumab) | Safety | Sensory neuropathy | Grade 3-4 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Sensory neuropathy | Did not have any | 16 Participants |
| Avastin (Bevacizumab) | Safety | Thrombosis/embolism | Grade 1-2 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Thrombosis/embolism | Grade 3-4 | 2 Participants |
| Avastin (Bevacizumab) | Safety | Thrombosis/embolism | Did not have any | 23 Participants |
| Avastin (Bevacizumab) | Safety | Renal failure | Grade 1-2 | 0 Participants |
| Avastin (Bevacizumab) | Safety | Renal failure | Grade 3-4 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Renal failure | Did not have any | 24 Participants |
| Avastin (Bevacizumab) | Safety | Fatigue | Grade 1-2 | 21 Participants |
| Avastin (Bevacizumab) | Safety | Fatigue | Grade 3-4 | 1 Participants |
| Avastin (Bevacizumab) | Safety | Fatigue | Did not have any | 3 Participants |