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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00722865
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 86
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma	Drug: Avastin	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Avastin (Bevacizumab) in Combination With ABVD for the Treatment of Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: Avastin (Bevacizumab) single-arm, open-label	Drug: 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.; Other Names: Bevacizumab

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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.

3. Overall Survival [2 years]

   Overall survival: patients are still alive.

4. Safety [2 years]

   Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Genentech, Inc.

Investigators

• Principal Investigator: Jeremy Abramson, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeremy Abramson, MD, Director, Lymphoma Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00722865
• Other Study ID Numbers: 07-388
• First Posted: Jul 28, 2008
• Last Update Posted: Oct 18, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Jeremy Abramson, MD, Director, Lymphoma Program, Massachusetts General Hospital: Avastin; bevacizumab; ABVD; angiogenesis; antiangiogenic; Hodgkin
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	25
COMPLETED	23
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
Overall Participants	25
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	29
Sex: Female, Male (Count of Participants)
Female	10 40%
Male	15 60%
Region of Enrollment (participants) [Number]
United States	25 100%
Stage of Cancer (Count of Participants)
Stage III	10 40%
Stage IV	15 60%
Hemoglobin (Count of Participants)
<10.5 g/dL	7 28%
>=10.5 g/dL	18 72%
Leukocytosis (Count of Participants)
>15,000/uL	5 20%
<=15,000/uL	20 80%
Absolute lymphocyte count (Count of Participants)
<600/uL	4 16%
>=600/uL	21 84%
Albumin (Count of Participants)
<4.0 g/dL	17 68%
>=4.0 g/dL	8 32%
B symptoms (Count of Participants)
Yes	15 60%
No	10 40%
International Prognostic Scoring System (IPSS) (Count of Participants)
0	1 4%
1	5 20%
2	5 20%
3	4 16%
4	7 28%
5	3 12%

Outcome Measures

1. Primary Outcome

Title	Failure-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
Measure Participants	25
at 2 years	67 268%
at median follow-up of 18 months	73 292%

2. Secondary Outcome

Title	Overall Response Rate Using the Modified Cheson Criteria
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
Measure Participants	25
Number (90% Confidence Interval) [percentage of participants]	96 384%

3. Secondary Outcome

Title	Progression-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
Measure Participants	25
at 2 years	67 268%
at median follow-up of 18 months	73 292%

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival: patients are still alive.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
Measure Participants	25
Count of Participants [Participants]	25 100%

5. Secondary Outcome

Title	Safety
Description	Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
Measure Participants	25
Grade 1-2	19 76%
Grade 3-4	3 12%
Did not have any	3 12%
Grade 1-2	1 4%
Grade 3-4	22 88%
Did not have any	2 8%
Grade 1-2	3 12%
Grade 3-4	0 0%
Did not have any	22 88%
Grade 1-2	0 0%
Grade 3-4	4 16%
Did not have any	21 84%
Grade 1-2	2 8%
Grade 3-4	1 4%
Did not have any	22 88%
Grade 1-2	0 0%
Grade 3-4	0 0%
Did not have any	25 100%
Grade 1-2	1 4%
Grade 3-4	1 4%
Did not have any	23 92%
Grade 1-2	1 4%
Grade 3-4	0 0%
Did not have any	24 96%
Grade 1-2	0 0%
Grade 3-4	1 4%
Did not have any	24 96%
Grade 1-2	4 16%
Grade 3-4	0 0%
Did not have any	21 84%
Grade 1-2	8 32%
Grade 3-4	1 4%
Did not have any	16 64%
Grade 1-2	0 0%
Grade 3-4	2 8%
Did not have any	23 92%
Grade 1-2	0 0%
Grade 3-4	1 4%
Did not have any	24 96%
Grade 1-2	21 84%
Grade 3-4	1 4%
Did not have any	3 12%

Adverse Events

Arm/Group Title	Avastin (Bevacizumab)
Arm/Group Description	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.
All Cause Mortality
	Avastin (Bevacizumab)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Avastin (Bevacizumab)
	Affected / at Risk (%)	# Events
Total	4/25 (16%)
Cardiac disorders
Pericardial Effusion	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Soft Tissue Necrosis	1/25 (4%)	1
Nervous system disorders
Sensory Neuropathy	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Avastin (Bevacizumab)
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Platelets	25/25 (100%)	165
Febrile neutropenia	25/25 (100%)	165
Leukocytosis	25/25 (100%)	165
Thrombotic thrombocytopenic purpura	25/25 (100%)	165
Nose- hemorrhage	3/25 (12%)	7
Cardiac disorders
Conduction disorder	3/25 (12%)	5
Hypertension	3/25 (12%)	5
Pericardial effusion (non-malignant)	2/25 (8%)	8
Myocarditis	2/25 (8%)	2
Gastrointestinal disorders
Ascites	25/25 (100%)	165
Vomiting	25/25 (100%)	165
Jejunal fistula	25/25 (100%)	165
Anal hemorrhage	14/25 (56%)	25
Gastritis	4/25 (16%)	5
Ileal obstruction	3/25 (12%)	5
Gastrointestinal disorders - Other, specify	2/25 (8%)	2
General disorders
Chills	25/25 (100%)	165
Head/headache	25/25 (100%)	165
Abdomen- pain	5/25 (20%)	12
Back- pain	5/25 (20%)	12
Edema face	4/25 (16%)	5
Extremity-limb- pain	4/25 (16%)	4
Death neonatal	3/25 (12%)	5
Neck- pain	3/25 (12%)	3
Fatigue	2/25 (8%)	3
Joint, pain	2/25 (8%)	3
Pain-other	2/25 (8%)	3
Chest wall, pain	2/25 (8%)	2
Throat/pharynx/larynx- pain	2/25 (8%)	2
Infections and infestations
Anorectal infection	4/25 (16%)	6
Infection Gr0-2 neut, upper airway	2/25 (8%)	3
Wound infection	2/25 (8%)	2
Infections and infestations - Other, specify	2/25 (8%)	2
Metabolism and nutrition disorders
Hypercalcemia	4/25 (16%)	14
Dehydration	3/25 (12%)	8
Alkalosis	2/25 (8%)	7
Hypokalemia	2/25 (8%)	2
Nervous system disorders
Movements involuntary	9/25 (36%)	23
Edema cerebral	3/25 (12%)	5
Respiratory, thoracic and mediastinal disorders
Bronchial stricture	7/25 (28%)	11
Bronchial obstruction	4/25 (16%)	9
Atelectasis	4/25 (16%)	7
Respiratory, thoracic and mediastinal disorders - Other, specify	2/25 (8%)	3
Skin and subcutaneous tissue disorders
Pain of skin	25/25 (100%)	165
Periorbital edema	3/25 (12%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.