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A Phase 3 Study of Brentuximab Vedotin (SGN-35) in Patients at High Risk of Residual Hodgkin Lymphoma Following Stem Cell Transplant (The AETHERA Trial)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01100502
Recruitment Status : Active, not recruiting
First Posted : April 9, 2010
Results First Posted : November 11, 2015
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Seattle Genetics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Disease, Hodgkin
Interventions Drug: brentuximab vedotin
Drug: placebo
Enrollment 329
Recruitment Details Apr 2010-Aug 2014
Pre-assignment Details  
Arm/Group Title Brentuximab Vedotin Placebo
Hide Arm/Group Description brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion placebo every 3 weeks by IV infusion
Period Title: Treatment Period
Started 165 164
Completed 78 81
Not Completed 87 83
Reason Not Completed
Adverse Event             54             10
Withdrawal by Subject             9             4
Progressive Disease             24             69
Period Title: Long-Term Follow-up
Started 165 [1] 164 [1]
Completed 28 [2] 25 [2]
Not Completed 137 139
Reason Not Completed
Withdrawal by Subject             10             8
Lost to Follow-up             5             2
Continuing in long-term follow-up             122             129
[1]
All participants were to be followed after treatment
[2]
Completed follow-up due to death
Arm/Group Title Brentuximab Vedotin Placebo Total
Hide Arm/Group Description brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion placebo every 3 weeks by IV infusion Total of all reporting groups
Overall Number of Baseline Participants 165 164 329
Hide Baseline Analysis Population Description
Intention-to-Treat analysis set
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 165 participants 164 participants 329 participants
33
(18 to 71)
32
(18 to 76)
32
(18 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 165 participants 164 participants 329 participants
Female
89
  53.9%
67
  40.9%
156
  47.4%
Male
76
  46.1%
97
  59.1%
173
  52.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 165 participants 164 participants 329 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   1.2%
3
   1.8%
5
   1.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
10
   6.1%
2
   1.2%
12
   3.6%
White
153
  92.7%
156
  95.1%
309
  93.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
3
   1.8%
3
   0.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 165 participants 164 participants 329 participants
Russian Federation 20 19 39
Romania 4 6 10
Hungary 9 11 20
United States 67 68 135
United Kingdom 3 3 6
Spain 4 6 10
Czech Republic 5 0 5
Poland 26 28 54
Italy 9 7 16
France 8 5 13
Serbia 3 6 9
Bulgaria 7 2 9
Germany 0 3 3
Eastern Cooperative Oncology Group Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 165 participants 164 participants 329 participants
0 87 97 184
1 77 67 144
2 1 0 1
[1]
Measure Description: 0=Normal activity; 1=Symptoms but ambulatory; 2=In bed <50% of the time; 3= In bed >50% of the time; 4=100% bedridden; 5=Dead
Hodgkin Lymphoma Status after end of Frontline Therapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 165 participants 164 participants 329 participants
Refractory 99 97 196
Relapse in less than 12 months 53 54 107
Relapse 12 months or later with extranodal disease 13 13 26
Best Response to Salvage Therapy pre-ASCT  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 165 participants 164 participants 329 participants
Complete remission 61 62 123
Partial remission 57 56 113
Stable disease 47 46 93
1.Primary Outcome
Title Progression-free Survival by Independent Review
Hide Description Time from date of randomization to the first documentation of disease progression by independent review or to death due to any cause, whichever comes first
Time Frame Up to approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-Treat analysis set
Arm/Group Title Brentuximab Vedotin Placebo
Hide Arm/Group Description:
brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
placebo every 3 weeks by IV infusion
Overall Number of Participants Analyzed 165 164
Median (95% Confidence Interval)
Unit of Measure: months
42.9
(30.4 to 42.9)
24.1 [1] 
(11.5 to NA)
[1]
Follow-up is not long enough to estimate an upper bound for median progression-free survival
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brentuximab Vedotin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.40 to 0.81
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival
Hide Description Time from date of randomization to date of death due to any cause
Time Frame Up to approximately 10 years
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Incidence of Adverse Events or Laboratory Abnormalities
Hide Description [Not Specified]
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set includes all patients who received at least 1 dose of brentuximab vedotin or only received placebo: 2 patients randomized to placebo received a single dose of brentuximab vedotin and are included in the brentuximab vedotin arm; 2 patients randomized to placebo received no study treatment and are not included in the analysis
Arm/Group Title Brentuximab Vedotin Placebo
Hide Arm/Group Description:
brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
placebo every 3 weeks by IV infusion
Overall Number of Participants Analyzed 167 160
Measure Type: Number
Unit of Measure: participants
Any Treatment-Emergent Adverse Event 163 142
Any Treatment-Related Adverse Event 147 79
Any Adverse Event with Severity >= Grade 3 93 51
Any Serious Adverse Event 41 20
Any Treatment-Related Serious Adverse Events 19 7
Treatment Discontinuation Due to Adverse Event 54 10
Any Laboratory Abnormalities Severity >=Grade 3 69 29
4.Secondary Outcome
Title Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin
Hide Description [Not Specified]
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
ATA-evaluable patients (patients with a baseline and at least 1 postbaseline sample)
Arm/Group Title Brentuximab Vedotin Placebo
Hide Arm/Group Description:
brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
placebo every 3 weeks by IV infusion
Overall Number of Participants Analyzed 157 154
Measure Type: Number
Unit of Measure: participants
Baseline Negative 138 142
Baseline Negative: -'ve Postbaseline 92 104
Baseline Negative: Transiently +'ve Postbaseline 36 27
Baseline Negative: Persistently +'ve Postbaseline 10 11
Baseline Positive 19 12
Baseline Positive: -'ve Postbaseline 7 0
Baseline Positive: Transiently +'ve Postbaseline 9 5
Baseline Positive: Persistently +'ve Postbaseline 3 7
Time Frame Up to 12 months
Adverse Event Reporting Description Safety Analysis Set includes all patients who received at least 1 dose of brentuximab vedotin or only received placebo: 2 patients randomized to placebo received a single dose of brentuximab vedotin and are included in the brentuximab vedotin arm; 2 patients randomized to placebo received no study treatment and are not included in the analysis
 
Arm/Group Title Placebo Brentuximab Vedotin
Hide Arm/Group Description placebo every 3 weeks by IV infusion brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
All-Cause Mortality
Placebo Brentuximab Vedotin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Brentuximab Vedotin
Affected / at Risk (%) Affected / at Risk (%)
Total   20/160 (12.50%)   41/167 (24.55%) 
Blood and lymphatic system disorders     
Bone marrow failure  1  1/160 (0.63%)  0/167 (0.00%) 
Neutropenia  1  1/160 (0.63%)  1/167 (0.60%) 
Thrombocytopenia  1  2/160 (1.25%)  0/167 (0.00%) 
Cardiac disorders     
Bradycardia  1  0/160 (0.00%)  1/167 (0.60%) 
Cardiac failure congestive  1  0/160 (0.00%)  1/167 (0.60%) 
Myocardial infarction  1  0/160 (0.00%)  1/167 (0.60%) 
Pericardial effusion  1  1/160 (0.63%)  0/167 (0.00%) 
Sinus tachycardia  1  0/160 (0.00%)  1/167 (0.60%) 
Gastrointestinal disorders     
Abdominal pain  1  1/160 (0.63%)  1/167 (0.60%) 
Constipation  1  0/160 (0.00%)  2/167 (1.20%) 
Diarrhoea  1  1/160 (0.63%)  1/167 (0.60%) 
Epigastric discomfort  1  0/160 (0.00%)  1/167 (0.60%) 
Erosive duodenitis  1  0/160 (0.00%)  1/167 (0.60%) 
Gastrointestinal haemorrhage  1  1/160 (0.63%)  0/167 (0.00%) 
Nausea  1  1/160 (0.63%)  4/167 (2.40%) 
Pancreatitis acute  1  0/160 (0.00%)  1/167 (0.60%) 
Vomiting  1  1/160 (0.63%)  5/167 (2.99%) 
General disorders     
Asthenia  1  0/160 (0.00%)  1/167 (0.60%) 
Disease progression  1  0/160 (0.00%)  1/167 (0.60%) 
Pyrexia  1  2/160 (1.25%)  6/167 (3.59%) 
Hepatobiliary disorders     
Hepatotoxicity  1  1/160 (0.63%)  3/167 (1.80%) 
Immune system disorders     
Hypersensitivity  1  0/160 (0.00%)  1/167 (0.60%) 
Infections and infestations     
Acute hepatitis b  1  0/160 (0.00%)  1/167 (0.60%) 
Appendicitis  1  0/160 (0.00%)  1/167 (0.60%) 
Hepatic candidiasis  1  0/160 (0.00%)  1/167 (0.60%) 
Herpes zoster  1  1/160 (0.63%)  2/167 (1.20%) 
Myelitis  1  0/160 (0.00%)  1/167 (0.60%) 
Pneumocystis jirovecii pneumonia  1  0/160 (0.00%)  1/167 (0.60%) 
Pneumonia  1  4/160 (2.50%)  7/167 (4.19%) 
Septic shock  1  1/160 (0.63%)  0/167 (0.00%) 
Sinusitis  1  1/160 (0.63%)  0/167 (0.00%) 
Upper respiratory tract infection  1  1/160 (0.63%)  1/167 (0.60%) 
Investigations     
Blood bilirubin increased  1  1/160 (0.63%)  0/167 (0.00%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  0/160 (0.00%)  1/167 (0.60%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  1/160 (0.63%)  0/167 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer  1  0/160 (0.00%)  1/167 (0.60%) 
Hodgkin's disease recurrent  1  1/160 (0.63%)  0/167 (0.00%) 
Mantle cell lymphoma  1  1/160 (0.63%)  0/167 (0.00%) 
Myelodysplastic syndrome  1  1/160 (0.63%)  1/167 (0.60%) 
Urethral papilloma  1  0/160 (0.00%)  1/167 (0.60%) 
Nervous system disorders     
Basilar migraine  1  0/160 (0.00%)  1/167 (0.60%) 
Encephalopathy  1  0/160 (0.00%)  1/167 (0.60%) 
Headache  1  0/160 (0.00%)  2/167 (1.20%) 
Neuralgia  1  0/160 (0.00%)  1/167 (0.60%) 
Peripheral motor neuropathy  1  0/160 (0.00%)  1/167 (0.60%) 
Peripheral sensory neuropathy  1  0/160 (0.00%)  3/167 (1.80%) 
Presyncope  1  0/160 (0.00%)  1/167 (0.60%) 
Syncope  1  0/160 (0.00%)  1/167 (0.60%) 
Psychiatric disorders     
Anxiety  1  1/160 (0.63%)  0/167 (0.00%) 
Depression  1  0/160 (0.00%)  1/167 (0.60%) 
Depression suicidal  1  1/160 (0.63%)  0/167 (0.00%) 
Suicidal ideation  1  0/160 (0.00%)  1/167 (0.60%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/160 (0.63%)  2/167 (1.20%) 
Asthma  1  1/160 (0.63%)  0/167 (0.00%) 
Bronchospasm  1  0/160 (0.00%)  1/167 (0.60%) 
Idiopathic pneumonia syndrome  1  1/160 (0.63%)  0/167 (0.00%) 
Lung infiltration  1  1/160 (0.63%)  0/167 (0.00%) 
Pneumonitis  1  0/160 (0.00%)  2/167 (1.20%) 
Pulmonary embolism  1  0/160 (0.00%)  1/167 (0.60%) 
Pulmonary toxicity  1  0/160 (0.00%)  1/167 (0.60%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  0/160 (0.00%)  1/167 (0.60%) 
Rash  1  0/160 (0.00%)  1/167 (0.60%) 
Vascular disorders     
Deep vein thrombosis  1  0/160 (0.00%)  1/167 (0.60%) 
Hypotension  1  0/160 (0.00%)  1/167 (0.60%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Brentuximab Vedotin
Affected / at Risk (%) Affected / at Risk (%)
Total   127/160 (79.38%)   151/167 (90.42%) 
Blood and lymphatic system disorders     
Anaemia  1  4/160 (2.50%)  14/167 (8.38%) 
Leukopenia  1  3/160 (1.88%)  9/167 (5.39%) 
Neutropenia  1  18/160 (11.25%)  58/167 (34.73%) 
Thrombocytopenia  1  3/160 (1.88%)  12/167 (7.19%) 
Cardiac disorders     
Sinus tachycardia  1  3/160 (1.88%)  9/167 (5.39%) 
Gastrointestinal disorders     
Abdominal pain  1  5/160 (3.13%)  22/167 (13.17%) 
Constipation  1  5/160 (3.13%)  20/167 (11.98%) 
Diarrhoea  1  15/160 (9.38%)  33/167 (19.76%) 
Dyspepsia  1  6/160 (3.75%)  11/167 (6.59%) 
Nausea  1  12/160 (7.50%)  35/167 (20.96%) 
Vomiting  1  11/160 (6.88%)  24/167 (14.37%) 
General disorders     
Asthenia  1  7/160 (4.38%)  13/167 (7.78%) 
Chills  1  8/160 (5.00%)  17/167 (10.18%) 
Fatigue  1  29/160 (18.13%)  40/167 (23.95%) 
Non-cardiac chest pain  1  9/160 (5.63%)  6/167 (3.59%) 
Oedema peripheral  1  10/160 (6.25%)  8/167 (4.79%) 
Pain  1  5/160 (3.13%)  9/167 (5.39%) 
Pyrexia  1  23/160 (14.37%)  26/167 (15.57%) 
Infections and infestations     
Bronchitis  1  10/160 (6.25%)  10/167 (5.99%) 
Herpes zoster  1  3/160 (1.88%)  10/167 (5.99%) 
Pharyngitis  1  4/160 (2.50%)  8/167 (4.79%) 
Sinusitis  1  10/160 (6.25%)  4/167 (2.40%) 
Upper respiratory tract infection  1  37/160 (23.13%)  43/167 (25.75%) 
Investigations     
Weight decreased  1  9/160 (5.63%)  32/167 (19.16%) 
Weight increased  1  14/160 (8.75%)  5/167 (2.99%) 
Metabolism and nutrition disorders     
Decreased appetite  1  9/160 (5.63%)  20/167 (11.98%) 
Hypokalaemia  1  6/160 (3.75%)  10/167 (5.99%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  15/160 (9.38%)  30/167 (17.96%) 
Back pain  1  16/160 (10.00%)  15/167 (8.98%) 
Muscle spasms  1  9/160 (5.63%)  18/167 (10.78%) 
Muscular weakness  1  1/160 (0.63%)  8/167 (4.79%) 
Myalgia  1  6/160 (3.75%)  18/167 (10.78%) 
Pain in extremity  1  8/160 (5.00%)  11/167 (6.59%) 
Nervous system disorders     
Headache  1  13/160 (8.13%)  19/167 (11.38%) 
Paraesthesia  1  2/160 (1.25%)  16/167 (9.58%) 
Peripheral motor neuropathy  1  3/160 (1.88%)  37/167 (22.16%) 
Peripheral sensory neuropathy  1  25/160 (15.63%)  91/167 (54.49%) 
Psychiatric disorders     
Anxiety  1  13/160 (8.13%)  14/167 (8.38%) 
Insomnia  1  5/160 (3.13%)  14/167 (8.38%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  26/160 (16.25%)  35/167 (20.96%) 
Dyspnoea  1  10/160 (6.25%)  21/167 (12.57%) 
Oropharyngeal pain  1  8/160 (5.00%)  9/167 (5.39%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  7/160 (4.38%)  10/167 (5.99%) 
Night sweats  1  18/160 (11.25%)  12/167 (7.19%) 
Pruritus  1  12/160 (7.50%)  19/167 (11.38%) 
Rash  1  5/160 (3.13%)  12/167 (7.19%) 
Vascular disorders     
Hypotension  1  4/160 (2.50%)  9/167 (5.39%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Patients are currently being followed for survival; final overall survival data are not available and will be reported upon study closure.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Seattle Genetics Inc.
Phone: (855)473-2436
Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT01100502     History of Changes
Other Study ID Numbers: SGN35-005
2009-016947-20 ( EudraCT Number )
First Submitted: April 6, 2010
First Posted: April 9, 2010
Results First Submitted: July 31, 2015
Results First Posted: November 11, 2015
Last Update Posted: March 19, 2019