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Brentuximab Vedotin Plus AVD in Limited-stage Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT01534078
Recruitment Status : Completed
First Posted : February 16, 2012
Results First Posted : August 30, 2017
Last Update Posted : February 20, 2018
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
H. Lee Moffitt Cancer Center and Research Institute
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Jeremy Abramson, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hodgkin Lymphoma
Interventions Drug: Brentuximab Vedotin
Drug: Adriamycin, vinblastine, and dacarbazine
Enrollment 34
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment Arm
Hide Arm/Group Description

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine (AVD)

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Period Title: Overall Study
Started 34
Completed 32
Not Completed 2
Reason Not Completed
Death             1
Withdrawal by Subject             1
Arm/Group Title Treatment Arm
Hide Arm/Group Description

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Overall Number of Baseline Participants 34
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 34 participants
36
(20 to 75)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
20 - 30 years Number Analyzed 34 participants
10
  29.4%
31 - 40 years Number Analyzed 34 participants
9
  26.5%
41 - 60 years Number Analyzed 34 participants
10
  29.4%
61 - 75 years Number Analyzed 34 participants
5
  14.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Female
17
  50.0%
Male
17
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
26
  76.5%
Unknown or Not Reported
8
  23.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
More Than One Race Number Analyzed 34 participants
1
   2.9%
Other Number Analyzed 34 participants
7
  20.6%
White Number Analyzed 34 participants
26
  76.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 34 participants
34
Stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
IA Number Analyzed 34 participants
6
  17.6%
IIA Number Analyzed 34 participants
24
  70.6%
IIB Number Analyzed 34 participants
4
  11.8%
[1]
Measure Description:

Lugano Classification of disease stage

  • Stage I: Found in only 1 lymph node or lymphoid organ or the cancer is found in only 1 area of a single organ outside the lymph system.
  • Stage II: The cancer is found in 2 or more lymph node areas on the same side of the diaphragm or the cancer extends locally from one lymph node area into a nearby organ

Can be assigned a letter A or B. B is when a patient has any of the following symptoms:

  • Loss of > than 10% of body weight over the previous 6 months without dieting
  • Unexplained fever of at least 100.4°F (38°C)
  • Drenching night sweats
Cellularity   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Hypercellular Number Analyzed 34 participants
1
   2.9%
Hypocellular Number Analyzed 34 participants
4
  11.8%
Normocellular Number Analyzed 34 participants
10
  29.4%
Missing Number Analyzed 34 participants
19
  55.9%
[1]
Measure Description: Hypercellular indicates more cells are being produce than expected, hypocellular means that fewer than expect number of cells are being produced, normocellular means an approximately normal amount of cells are being produced
Histology   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Classical Hodgkin Lymphoma, NOS Number Analyzed 34 participants
8
  23.5%
Lymphocytic Rich Number Analyzed 34 participants
4
  11.8%
Mixed Cellularity Number Analyzed 34 participants
4
  11.8%
Nodular Sclerosis Number Analyzed 34 participants
18
  52.9%
[1]
Measure Description:

The histological subtypes of classic Hodgkin lymphoma:

  • Classical NOS: Not Otherwise Specified (specific subtype not identified)
  • Lymphocyte-Rich: Rarely found in more than a few lymph nodes and usually occurs in the upper half of the body
  • Mixed Cellularity: Seen predominantly in adults, this is the second most common type. It can start in any lymph node but most often occurs in the upper half of the body.
  • Nodular Sclerosis: The most common type in developed countries. This most common in teens and young adults. Tends to start in lymph nodes in the chest or neck.
Risk Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Early Favorable Number Analyzed 34 participants
21
  61.8%
Early Unfavorable Number Analyzed 34 participants
13
  38.2%
[1]
Measure Description:

Early Unfavorable: Stage I or II disease and one or more of the following risk factors:

  • B Symptoms (see stage description)
  • Extranodal disease
  • Bulky disease (≥10 cm or >33% of the chest diameter on chest x-ray)
  • Three or more sites of nodal involvement
  • Sedimentation rate of ≥50 mm/h

Early Favorable: Stage I or II disease with none of the risk factors listed above. Patients with favorable classification tend to have better outcomes.

Number of Lesions   [1] 
Median (Full Range)
Unit of measure:  Lesions
Number Analyzed 33 participants
5
(1 to 6)
[1]
Measure Analysis Population Description: Information is missing for one participant
Longest Tumor Diameter   [1] 
Median (Full Range)
Unit of measure:  Centimeters (cm)
Number Analyzed 33 participants
33.4
(15.1 to 83.3)
[1]
Measure Analysis Population Description: Information is missing for one participant
1.Primary Outcome
Title Complete Response Rate
Hide Description Complete response rate at the end of therapy as measured by Positron emission tomography–computed tomography (PET/CT). Response is evaluated using Revised International Working Group Criteria. Complete response is defined as disappearance of all evidence of disease.
Time Frame End of Therapy (median duration of four months)
Hide Outcome Measure Data
Hide Analysis Population Description
Two participants were not evaluated for response due to a death and a withdrawal.
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Overall Number of Participants Analyzed 32
Measure Type: Count of Participants
Unit of Measure: Participants
31
  96.9%
2.Secondary Outcome
Title Overall Response Rate After One Cycle of Brentuximab
Hide Description

The number of participants achieving a Partial Response (PR) or Complete Response (CR) after one cycle of Brentuximab monotherapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria.

  • CR: Disappearance of all evidence of disease
  • PR: Regression of measurable disease and no new sites
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Overall Number of Participants Analyzed 34
Measure Type: Count of Participants
Unit of Measure: Participants
18
  52.9%
3.Secondary Outcome
Title Overall Response Rate
Hide Description

The number of participants achieving a Partial Response (PR) or Complete Response (CR) at the end of therapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria.

  • CR: Disappearance of all evidence of disease
  • PR: Regression of measurable disease and no new sites
Time Frame End of Therapy (median duration of four months)
Hide Outcome Measure Data
Hide Analysis Population Description
Two participants were not evaluated for response due to a death and a withdrawal.
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Overall Number of Participants Analyzed 32
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
31
  96.9%
Partial Response
0
   0.0%
4.Secondary Outcome
Title Grade III or IV Adverse Events
Hide Description A summary of the grade 3 or 4 adverse events experienced by participants as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The data is shown as the number of participants that experienced at least one grade 3 or 4 adverse event for each of the specified toxicities.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Overall Number of Participants Analyzed 34
Measure Type: Number
Unit of Measure: participants
Peripheral sensory neuropathy 8
Neutrophil count decreased 21
Fatigue 3
Nausea 1
Anemia 2
White blood cell decreased 6
Abdominal pain 2
Diarrhea 1
Febrile neutropenia 12
Vomiting 1
Mucositis oral 1
Weight loss 2
Dehydration 1
Hypertension 1
Infections and infestations - Other, specify 1
Blood and lymphatic system disorders - Other, spec 1
Time Frame From the start of therapy until the the end of followup due to disease progression, death, or withdrawal from the study. Median follow-up duration of 38 months.
Adverse Event Reporting Description Adverse events were assessed with regularly scheduled physical exams, laboratory tests, and participant self reports.
 
Arm/Group Title Treatment Arm
Hide Arm/Group Description

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

All-Cause Mortality
Treatment Arm
Affected / at Risk (%)
Total   1/34 (2.94%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment Arm
Affected / at Risk (%) # Events
Total   15/34 (44.12%)    
Blood and lymphatic system disorders   
Febrile Neutropenia  1  8/34 (23.53%)  8
Cardiac disorders   
Chest Pain - Cardiac  1  1/34 (2.94%)  1
Gastrointestinal disorders   
Viral Gastritis  1  1/34 (2.94%)  1
Abdominal Pain  1  2/34 (5.88%)  2
Gastric Hemorrhage  1  1/34 (2.94%)  1
Ileus  1  1/34 (2.94%)  1
Nausea, Vomiting, Dehydration  1  1/34 (2.94%)  1
Anorexia, Nausea, Vomiting  1  1/34 (2.94%)  1
Diarrhea, Hypotension  1  1/34 (2.94%)  1
Ileus, Esophagitis, Transaminase elevation, low white blood cell count, dehydration  1  1/34 (2.94%)  1
General disorders   
Fever  1  1/34 (2.94%)  1
Fever, Sinus Congestion  1  1/34 (2.94%)  1
Infections and infestations   
Sepsis  1  1/34 (2.94%)  1
Bronchial Infection  1  1/34 (2.94%)  1
Line Infection  1  1/34 (2.94%)  1
Soft Tissue Infection  1  1/34 (2.94%)  1
Investigations   
Neutrophil Count Decreased  1  2/34 (5.88%)  2
White Blood Cell Decreased  1  1/34 (2.94%)  2
Metabolism and nutrition disorders   
Dehydration  1  1/34 (2.94%)  1
Anorexia, Fatigue  1  1/34 (2.94%)  1
Musculoskeletal and connective tissue disorders   
Hip pain, back pain  1  1/34 (2.94%)  1
Psychiatric disorders   
Confusion  1  1/34 (2.94%)  1
Respiratory, thoracic and mediastinal disorders   
Aspiration  1  1/34 (2.94%)  1
Skin and subcutaneous tissue disorders   
Hidradenitis Suppurativa  1  1/34 (2.94%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment Arm
Affected / at Risk (%) # Events
Total   34/34 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  27/34 (79.41%)  52
Febrile neutropenia  1  6/34 (17.65%)  6
Leukocytosis  1  3/34 (8.82%)  5
Cardiac disorders   
Sinus tachycardia  1  2/34 (5.88%)  4
Ear and labyrinth disorders   
Tinnitus  1  5/34 (14.71%)  5
Endocrine disorders   
Endocrine disorders - Other, specify  1  2/34 (5.88%)  2
Gastrointestinal disorders   
Abdominal pain  1  14/34 (41.18%)  24
Bloating  1  2/34 (5.88%)  2
Colitis  1  2/34 (5.88%)  2
Constipation  1  26/34 (76.47%)  35
Diarrhea  1  15/34 (44.12%)  25
Dry mouth  1  2/34 (5.88%)  2
Gastritis  1  2/34 (5.88%)  2
Gastroesophageal reflux disease  1  7/34 (20.59%)  8
Hemorrhoids  1  4/34 (11.76%)  4
Mucositis oral  1  8/34 (23.53%)  8
Nausea  1  26/34 (76.47%)  41
Oral pain  1  4/34 (11.76%)  4
Rectal hemorrhage  1  2/34 (5.88%)  2
Vomiting  1  12/34 (35.29%)  18
Gastrointestinal disorders - Other, specify  1  5/34 (14.71%)  8
General disorders   
Edema limbs  1  2/34 (5.88%)  2
Fatigue  1  30/34 (88.24%)  53
Fever  1  4/34 (11.76%)  6
Infusion related reaction  1  3/34 (8.82%)  5
Malaise  1  2/34 (5.88%)  2
Pain  1  8/34 (23.53%)  14
General disorders and administration site conditions - Other,  1  3/34 (8.82%)  4
Infections and infestations   
Upper respiratory infection  1  5/34 (14.71%)  7
Urinary tract infection  1  2/34 (5.88%)  2
Infections and infestations - Other, specify  1  4/34 (11.76%)  6
Injury, poisoning and procedural complications   
Injury, poisoning and procedural complications - Other, specify  1  2/34 (5.88%)  2
Investigations   
Alanine aminotransferase increased  1  14/34 (41.18%)  21
Alkaline phosphatase increased  1  2/34 (5.88%)  3
Aspartate aminotransferase increased  1  10/34 (29.41%)  14
Neutrophil count decreased  1  26/34 (76.47%)  74
Platelet count decreased  1  6/34 (17.65%)  10
Weight loss  1  7/34 (20.59%)  14
White blood cell decreased  1  21/34 (61.76%)  56
Investigations - Other, specify  1  2/34 (5.88%)  2
Metabolism and nutrition disorders   
Anorexia  1  9/34 (26.47%)  11
Dehydration  1  5/34 (14.71%)  7
Hyperglycemia  1  14/34 (41.18%)  17
Hypokalemia  1  3/34 (8.82%)  3
Musculoskeletal and connective tissue disorders   
Arthralgia  1  9/34 (26.47%)  12
Back pain  1  7/34 (20.59%)  7
Bone pain  1  14/34 (41.18%)  21
Generalized muscle weakness  1  6/34 (17.65%)  6
Myalgia  1  6/34 (17.65%)  8
Pain in extremity  1  5/34 (14.71%)  8
Musculoskeletal and connective tissue disorder -  1  9/34 (26.47%)  13
Nervous system disorders   
Dizziness  1  9/34 (26.47%)  9
Headache  1  9/34 (26.47%)  10
Memory impairment  1  2/34 (5.88%)  2
Peripheral motor neuropathy  1  7/34 (20.59%)  11
Peripheral sensory neuropathy  1  27/34 (79.41%)  67
Nervous system disorders - Other, specify  1  3/34 (8.82%)  5
Psychiatric disorders   
Anxiety  1  7/34 (20.59%)  8
Depression  1  4/34 (11.76%)  4
Insomnia  1  12/34 (35.29%)  14
Restlessness  1  2/34 (5.88%)  2
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  2/34 (5.88%)  2
Cough  1  8/34 (23.53%)  11
Dyspnea  1  5/34 (14.71%)  5
Nasal congestion  1  2/34 (5.88%)  2
Sore throat  1  3/34 (8.82%)  3
Respiratory, thoracic and mediastinal disorders - Other, specify  1  4/34 (11.76%)  4
Skin and subcutaneous tissue disorders   
Alopecia  1  16/34 (47.06%)  21
Erythema multiforme  1  2/34 (5.88%)  3
Hyperhidrosis  1  6/34 (17.65%)  6
Pruritus  1  7/34 (20.59%)  8
Rash acneiform  1  5/34 (14.71%)  6
Rash maculo-papular  1  8/34 (23.53%)  9
Skin hyperpigmentation  1  2/34 (5.88%)  2
Skin and subcutaneous tissue disorders - Other, specify  1  8/34 (23.53%)  12
Vascular disorders   
Flushing  1  2/34 (5.88%)  2
Hot flashes  1  3/34 (8.82%)  3
Hypertension  1  12/34 (35.29%)  31
Hypotension  1  2/34 (5.88%)  3
Thromboembolic event  1  2/34 (5.88%)  2
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Jeremy Abramson, MD
Organization: Massachusetts General Hospital
Phone: 617-724-4000
Responsible Party: Jeremy Abramson, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01534078     History of Changes
Other Study ID Numbers: 11-462
First Submitted: February 9, 2012
First Posted: February 16, 2012
Results First Submitted: June 7, 2017
Results First Posted: August 30, 2017
Last Update Posted: February 20, 2018