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A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE™)

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: NCT01578707
Recruitment Status : Completed
First Posted : April 17, 2012
Results First Posted : October 12, 2015
Last Update Posted : December 18, 2019
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Relapsed or Refractory Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Interventions Drug: ofatumumab
Drug: ibrutinib
Enrollment 391
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Period Title: Overall Study
Started 196 195
Completed 196 195
Not Completed 0 0
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B) Total
Hide Arm/Group Description

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Total of all reporting groups
Overall Number of Baseline Participants 196 195 391
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 196 participants 195 participants 391 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
75
  38.3%
77
  39.5%
152
  38.9%
>=65 years
121
  61.7%
118
  60.5%
239
  61.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 196 participants 195 participants 391 participants
66.8  (8.88) 66.1  (10.15) 66.5  (9.53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 196 participants 195 participants 391 participants
Female
59
  30.1%
66
  33.8%
125
  32.0%
Male
137
  69.9%
129
  66.2%
266
  68.0%
1.Primary Outcome
Title PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013
Hide Description The primary objective of this study was to evaluate the efficacy of ibrutinib compared to ofatumumab based on independent review committee (IRC) assessment of progression-free survival (PFS) according to 2008 IWCLL guidelines.
Time Frame Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description:

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Overall Number of Participants Analyzed 196 195
Median (95% Confidence Interval)
Unit of Measure: months
8.1
(7.2 to 8.3)
NA [1] 
(NA to NA)
[1]
IBR: Median PFS was not reached so 95% CI for median PFS is not applicable.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab (Arm A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Overall Response Rate (ORR) by Independent Review Committee (IRC)
Hide Description Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, limited to the time of primary analysis 06 November 2013
Time Frame About 18 months after the first subject was enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description:

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Overall Number of Participants Analyzed 196 195
Measure Type: Number
Unit of Measure: percentage of participants
4.1 42.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab (Arm A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title OS (Overall Survival)
Hide Description OS analysis was conducted at the time of study closure, with no adjustment for crossover from the ofatumumab arm to the ibrutinib arm
Time Frame OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description:

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Overall Number of Participants Analyzed 196 195
Median (95% Confidence Interval)
Unit of Measure: months
65.1 [1] 
(50.6 to NA)
67.7 [2] 
(61.0 to NA)
[1]
OFA: Upper limit of 95% CI for median OS is not estimable due to sparse events in the data / insufficient number of participants with events.
[2]
IBR: Upper limit of 95% CI for median OS is not estimable due to sparse events in the data / insufficient number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab (Arm A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1653
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Rate of Sustained Hemoglobin and Platelet Improvement
Hide Description Proportion of subjects with hemoglobin (HgB) increase >=20 g/L and platelet (PLT) increase >=50% over baseline continuously for >=56 days without blood transfusions or growth factors.
Time Frame From study initiation to study closure, including up to 6 years of study follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description:

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Overall Number of Participants Analyzed 196 195
Measure Type: Number
Unit of Measure: percentage of participants
Hgb Improvement in patient with baseline anemia 32.6 69.7
Platelet improvement in baseline thrombocytopenia 9.4 78.4
5.Other Pre-specified Outcome
Title Progression Free Survival (PFS) by Investigator With up to 6 Years of Study Follow-up
Hide Description Long-Term Progression Free Survival as assessed by the investigator with up to 6 years of study follow-up
Time Frame From study initiation to study closure, including up to 6 years of study follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description:

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Overall Number of Participants Analyzed 196 195
Median (95% Confidence Interval)
Unit of Measure: months
8.1
(7.79 to 8.25)
44.1
(38.47 to 56.18)
6.Other Pre-specified Outcome
Title Overall Response Rate (ORR) by Investigator
Hide Description Overall response per the IWCLL 2008 criteria as assessed by Investigator with up to 6 years of study follow-up
Time Frame From study initiation to study closure, including up to 6 years of study follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description:

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Overall Number of Participants Analyzed 196 195
Measure Type: Number
Unit of Measure: percentage of participants
22.4 87.7
Time Frame From first dose of study drug to within 30 days of last dose.
Adverse Event Reporting Description 196 subjects were randomized to the Ofa arm with 191 received drug thus 5 patients were not included in the number of participants at risk.
 
Arm/Group Title Ofatumumab (Arm A) Ibrutinib (Arm B)
Hide Arm/Group Description

An anti-CD20 monoclonal antibody

ofatumumab: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.

Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

A Bruton Tyrosine Kinase Inhibitor

ibrutinib: ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

All-Cause Mortality
Ofatumumab (Arm A) Ibrutinib (Arm B)
Affected / at Risk (%) Affected / at Risk (%)
Total   16/191 (8.38%)   24/195 (12.31%) 
Hide Serious Adverse Events
Ofatumumab (Arm A) Ibrutinib (Arm B)
Affected / at Risk (%) Affected / at Risk (%)
Total   59/191 (30.89%)   141/195 (72.31%) 
Blood and lymphatic system disorders     
Febrile Neutropenia * 1  4/191 (2.09%)  7/195 (3.59%) 
Anaemia * 1  4/191 (2.09%)  5/195 (2.56%) 
Neutropenia * 1  2/191 (1.05%)  4/195 (2.05%) 
Spontaneous Haematoma * 1  0/191 (0.00%)  2/195 (1.03%) 
Lymphadenopathy * 1  0/191 (0.00%)  1/195 (0.51%) 
Thrombocytopenia * 1  0/191 (0.00%)  1/195 (0.51%) 
Autoimmune Haemolytic Anaemia * 1  1/191 (0.52%)  0/195 (0.00%) 
Haemolytic Anaemia * 1  1/191 (0.52%)  0/195 (0.00%) 
Methaemoglobinaemia * 1  1/191 (0.52%)  0/195 (0.00%) 
Cardiac disorders     
Atrial Fibrillation * 1  1/191 (0.52%)  11/195 (5.64%) 
Cardiac Failure Congestive * 1  0/191 (0.00%)  3/195 (1.54%) 
Atrioventricular Block * 1  0/191 (0.00%)  2/195 (1.03%) 
Cardiac Failure * 1  1/191 (0.52%)  2/195 (1.03%) 
Myocardial infarction * 1  1/191 (0.52%)  2/195 (1.03%) 
Acute myocardial infarction * 1  1/191 (0.52%)  1/195 (0.51%) 
Angina Pectoris * 1  0/191 (0.00%)  1/195 (0.51%) 
Aortic Valve Disease * 1  0/191 (0.00%)  1/195 (0.51%) 
Atrial Tachycardia * 1  0/191 (0.00%)  1/195 (0.51%) 
Bradycardia * 1  0/191 (0.00%)  1/195 (0.51%) 
Cardiac Arrest * 1  0/191 (0.00%)  1/195 (0.51%) 
Myocardial Ischaemia * 1  0/191 (0.00%)  1/195 (0.51%) 
Palpitations * 1  0/191 (0.00%)  1/195 (0.51%) 
Pericardial Effusion * 1  0/191 (0.00%)  1/195 (0.51%) 
Supraventricular Tachycardia * 1  1/191 (0.52%)  1/195 (0.51%) 
Sinus Tachycardia * 1  1/191 (0.52%)  0/195 (0.00%) 
Ear and labyrinth disorders     
Hypoacusis * 1  0/191 (0.00%)  1/195 (0.51%) 
Eye disorders     
Vitreous Haemorrhage * 1  0/191 (0.00%)  1/195 (0.51%) 
Gastrointestinal disorders     
Diarrhoea * 1  1/191 (0.52%)  6/195 (3.08%) 
Vomiting * 1  0/191 (0.00%)  5/195 (2.56%) 
Abdominal Pain * 1  1/191 (0.52%)  4/195 (2.05%) 
Nausea * 1  0/191 (0.00%)  3/195 (1.54%) 
Umbilical Hernia * 1  0/191 (0.00%)  2/195 (1.03%) 
Upper Gastrointestinal Haemorrhage * 1  0/191 (0.00%)  2/195 (1.03%) 
Abdominal Pain Upper * 1  0/191 (0.00%)  1/195 (0.51%) 
Anorectal Discomfort * 1  0/191 (0.00%)  1/195 (0.51%) 
Duodenal Perforation * 1  0/191 (0.00%)  1/195 (0.51%) 
Dysphagia * 1  0/191 (0.00%)  1/195 (0.51%) 
Enteritis * 1  0/191 (0.00%)  1/195 (0.51%) 
Intestinal Obstruction * 1  0/191 (0.00%)  1/195 (0.51%) 
Large Intestinal Obstruction * 1  0/191 (0.00%)  1/195 (0.51%) 
Mucous stools * 1  0/191 (0.00%)  1/195 (0.51%) 
Oesophageal Obstruction * 1  0/191 (0.00%)  1/195 (0.51%) 
Oesophageal spasm * 1  0/191 (0.00%)  1/195 (0.51%) 
Pancreatitis * 1  0/191 (0.00%)  1/195 (0.51%) 
Poor Dental Condition * 1  0/191 (0.00%)  1/195 (0.51%) 
Rectal haemorrhage * 1  0/191 (0.00%)  1/195 (0.51%) 
Stomatitis * 1  0/191 (0.00%)  1/195 (0.51%) 
Constipation * 1  1/191 (0.52%)  0/195 (0.00%) 
Malabsorption * 1  1/191 (0.52%)  0/195 (0.00%) 
General disorders     
Pyrexia * 1  4/191 (2.09%)  15/195 (7.69%) 
Non-Cardiac Chest Pain * 1  0/191 (0.00%)  3/195 (1.54%) 
Malaise * 1  0/191 (0.00%)  2/195 (1.03%) 
Sudden Death * 1  0/191 (0.00%)  2/195 (1.03%) 
Asthenia * 1  0/191 (0.00%)  1/195 (0.51%) 
Catheter Site Pain * 1  0/191 (0.00%)  1/195 (0.51%) 
Chills * 1  0/191 (0.00%)  1/195 (0.51%) 
Cyst * 1  0/191 (0.00%)  1/195 (0.51%) 
Fatigue * 1  0/191 (0.00%)  1/195 (0.51%) 
General Physical Health Deterioration * 1  0/191 (0.00%)  1/195 (0.51%) 
Influenza Like Illness * 1  0/191 (0.00%)  1/195 (0.51%) 
Injection Site Extravasation * 1  0/191 (0.00%)  1/195 (0.51%) 
Effusion * 1  1/191 (0.52%)  0/195 (0.00%) 
Hepatobiliary disorders     
Cholecystitis * 1  0/191 (0.00%)  1/195 (0.51%) 
Cholestasis * 1  0/191 (0.00%)  1/195 (0.51%) 
Immune system disorders     
Anaphylactic Shock * 1  1/191 (0.52%)  0/195 (0.00%) 
Infections and infestations     
Pneumonia * 1  12/191 (6.28%)  42/195 (21.54%) 
Urinary Tract Infection * 1  0/191 (0.00%)  9/195 (4.62%) 
Cellulitis * 1  1/191 (0.52%)  8/195 (4.10%) 
Sepsis * 1  2/191 (1.05%)  8/195 (4.10%) 
Lung Infection * 1  0/191 (0.00%)  7/195 (3.59%) 
Escherichia Urinary Tract Infection * 1  0/191 (0.00%)  4/195 (2.05%) 
Lower Respiratory Tract Infection * 1  2/191 (1.05%)  4/195 (2.05%) 
Upper Respiratory Tract Infection * 1  4/191 (2.09%)  4/195 (2.05%) 
Infection * 1  1/191 (0.52%)  3/195 (1.54%) 
Aspergillus Infection * 1  0/191 (0.00%)  2/195 (1.03%) 
Bronchitis * 1  2/191 (1.05%)  2/195 (1.03%) 
Bronchopulmonary Aspergillosis * 1  0/191 (0.00%)  2/195 (1.03%) 
Gastroenteritis * 1  0/191 (0.00%)  2/195 (1.03%) 
Gastroenteritis Viral * 1  0/191 (0.00%)  2/195 (1.03%) 
Herpes Zoster * 1  1/191 (0.52%)  2/195 (1.03%) 
Influenza * 1  2/191 (1.05%)  2/195 (1.03%) 
Neutropenic Sepsis * 1  2/191 (1.05%)  2/195 (1.03%) 
Pneumocystis Jirovecii Ppneumonia * 1  1/191 (0.52%)  2/195 (1.03%) 
Pneumonia Pseudomonal * 1  1/191 (0.52%)  2/195 (1.03%) 
Pneumonia Staphylococcal * 1  0/191 (0.00%)  2/195 (1.03%) 
Sinusitis * 1  0/191 (0.00%)  2/195 (1.03%) 
Urosepsis * 1  0/191 (0.00%)  2/195 (1.03%) 
Bacteraemia * 1  2/191 (1.05%)  1/195 (0.51%) 
Bacterial Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Bacteroides Bacteraemia * 1  0/191 (0.00%)  1/195 (0.51%) 
Bronchitis Bacterial * 1  0/191 (0.00%)  1/195 (0.51%) 
Campylobacter Gastroenteritis * 1  0/191 (0.00%)  1/195 (0.51%) 
Clostridium Difficile Colitis * 1  0/191 (0.00%)  1/195 (0.51%) 
Clostridium Difficile Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Empyema * 1  0/191 (0.00%)  1/195 (0.51%) 
Enterococcal Iinfection * 1  0/191 (0.00%)  1/195 (0.51%) 
Enterococcal Sepsis * 1  0/191 (0.00%)  1/195 (0.51%) 
Enterocolitis Infectious * 1  0/191 (0.00%)  1/195 (0.51%) 
Folliculitis * 1  1/191 (0.52%)  1/195 (0.51%) 
Gastrointestinal Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
H1N1 Influenza * 1  0/191 (0.00%)  1/195 (0.51%) 
Haemophilus Bacteraemia * 1  0/191 (0.00%)  1/195 (0.51%) 
Haemophilus Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Haemophilus Sepsis * 1  0/191 (0.00%)  1/195 (0.51%) 
Herpes Virus Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Impetigo * 1  0/191 (0.00%)  1/195 (0.51%) 
Infective Exacerbation of Bronchiectasis * 1  0/191 (0.00%)  1/195 (0.51%) 
Intervertebral Discitis * 1  0/191 (0.00%)  1/195 (0.51%) 
Lower Respiratory Tract Infection Bacterial * 1  0/191 (0.00%)  1/195 (0.51%) 
Lymph Gland Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Meningitis Pneumococcal * 1  0/191 (0.00%)  1/195 (0.51%) 
Mycobacterium Avium Complex Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Osteomyelitis * 1  0/191 (0.00%)  1/195 (0.51%) 
Otitis Externa * 1  0/191 (0.00%)  1/195 (0.51%) 
Otitis Media * 1  0/191 (0.00%)  1/195 (0.51%) 
Parainfluenzae Virus Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Pneumococcal Sepsis * 1  0/191 (0.00%)  1/195 (0.51%) 
Pneumocystis Jirovecii Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Pneumonia Bacterial * 1  1/191 (0.52%)  1/195 (0.51%) 
Pneumonia Respiratory Syncytial Viral * 1  0/191 (0.00%)  1/195 (0.51%) 
Pneumonia viral * 1  0/191 (0.00%)  1/195 (0.51%) 
Pseudomonal Sepsis * 1  0/191 (0.00%)  1/195 (0.51%) 
Pseudomonas Infection * 1  2/191 (1.05%)  1/195 (0.51%) 
Pyelonephritis * 1  0/191 (0.00%)  1/195 (0.51%) 
Respiratory Tract Infection * 1  2/191 (1.05%)  1/195 (0.51%) 
Rhinovirus Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Septic Shock * 1  1/191 (0.52%)  1/195 (0.51%) 
Staphylococcal Sepsis * 1  0/191 (0.00%)  1/195 (0.51%) 
Staphylococcal Skin Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Tonsillitis Fungal * 1  0/191 (0.00%)  1/195 (0.51%) 
Tooth Infection * 1  0/191 (0.00%)  1/195 (0.51%) 
Urethritis * 1  0/191 (0.00%)  1/195 (0.51%) 
Urinary Tract Infection Pseudomonal * 1  0/191 (0.00%)  1/195 (0.51%) 
Viral Pharyngitis * 1  0/191 (0.00%)  1/195 (0.51%) 
Abscess Limb * 1  1/191 (0.52%)  0/195 (0.00%) 
Anal Infection * 1  1/191 (0.52%)  0/195 (0.00%) 
Breast Cellulitis * 1  1/191 (0.52%)  0/195 (0.00%) 
Febrile Infection * 1  1/191 (0.52%)  0/195 (0.00%) 
Herpes Simplex * 1  1/191 (0.52%)  0/195 (0.00%) 
Infectious Pleural Effusion * 1  1/191 (0.52%)  0/195 (0.00%) 
Lung Infection Pseudomonal * 1  1/191 (0.52%)  0/195 (0.00%) 
Nocardiosis * 1  1/191 (0.52%)  0/195 (0.00%) 
Ophthalmic Herpes Zoster * 1  1/191 (0.52%)  0/195 (0.00%) 
Pneumonia Mycoplasmal * 1  1/191 (0.52%)  0/195 (0.00%) 
Sepsis Syndrome * 1  1/191 (0.52%)  0/195 (0.00%) 
Stenotrophomonas Infection * 1  2/191 (1.05%)  0/195 (0.00%) 
Injury, poisoning and procedural complications     
Subdural Haematoma * 1  0/191 (0.00%)  6/195 (3.08%) 
Femur Fracture * 1  0/191 (0.00%)  4/195 (2.05%) 
Fall * 1  0/191 (0.00%)  2/195 (1.03%) 
Hip Fracture * 1  0/191 (0.00%)  2/195 (1.03%) 
Arthropod Bite * 1  0/191 (0.00%)  1/195 (0.51%) 
Brain Contusion * 1  0/191 (0.00%)  1/195 (0.51%) 
Burns Third Degree * 1  0/191 (0.00%)  1/195 (0.51%) 
Femoral Neck Fracture * 1  0/191 (0.00%)  1/195 (0.51%) 
Laceration * 1  0/191 (0.00%)  1/195 (0.51%) 
Multiple Fractures * 1  1/191 (0.52%)  1/195 (0.51%) 
Post Procedural Haemorrhage * 1  0/191 (0.00%)  1/195 (0.51%) 
Rib Fracture * 1  0/191 (0.00%)  1/195 (0.51%) 
Spinal Compression Fracture * 1  1/191 (0.52%)  1/195 (0.51%) 
Subarachnoid Haematoma * 1  0/191 (0.00%)  1/195 (0.51%) 
Subarachnoid Haemorrhage * 1  0/191 (0.00%)  1/195 (0.51%) 
Subdural Haemorrhage * 1  0/191 (0.00%)  1/195 (0.51%) 
Toxicity to Various Agents * 1  0/191 (0.00%)  1/195 (0.51%) 
Traumatic Haematoma * 1  0/191 (0.00%)  1/195 (0.51%) 
Infusion Related Reaction * 1  2/191 (1.05%)  0/195 (0.00%) 
Muscle Strain * 1  1/191 (0.52%)  0/195 (0.00%) 
Investigations     
Immunoglobulins Decreased * 1  0/191 (0.00%)  1/195 (0.51%) 
Metabolism and nutrition disorders     
Hyponatraemia * 1  0/191 (0.00%)  3/195 (1.54%) 
Hypercalcaemia * 1  0/191 (0.00%)  2/195 (1.03%) 
Dehydration * 1  0/191 (0.00%)  1/195 (0.51%) 
Hypokalaemia * 1  0/191 (0.00%)  1/195 (0.51%) 
Iron Deficiency * 1  0/191 (0.00%)  1/195 (0.51%) 
Tumour Lysis Syndrome * 1  1/191 (0.52%)  1/195 (0.51%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  0/191 (0.00%)  4/195 (2.05%) 
Arthritis * 1  0/191 (0.00%)  2/195 (1.03%) 
Pain in Extremity * 1  0/191 (0.00%)  2/195 (1.03%) 
Arthralgia * 1  0/191 (0.00%)  1/195 (0.51%) 
Bone Pain * 1  1/191 (0.52%)  1/195 (0.51%) 
Muscular Weakness * 1  0/191 (0.00%)  1/195 (0.51%) 
Myalgia * 1  0/191 (0.00%)  1/195 (0.51%) 
Pathological Fracture * 1  0/191 (0.00%)  1/195 (0.51%) 
Spinal Column Stenosis * 1  0/191 (0.00%)  1/195 (0.51%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Chronic Lymphocytic Leukaemia * 1  3/191 (1.57%)  5/195 (2.56%) 
Basal Cell Carcinoma * 1  0/191 (0.00%)  3/195 (1.54%) 
Richter's Syndrome * 1  0/191 (0.00%)  3/195 (1.54%) 
Hodgkin's Disease * 1  0/191 (0.00%)  2/195 (1.03%) 
Lung Adenocarcinoma * 1  0/191 (0.00%)  2/195 (1.03%) 
Prostate Cancer * 1  0/191 (0.00%)  2/195 (1.03%) 
Adenocarcinoma * 1  0/191 (0.00%)  1/195 (0.51%) 
Bone Cancer Metastatic * 1  0/191 (0.00%)  1/195 (0.51%) 
Brain Neoplasm Malignant * 1  0/191 (0.00%)  1/195 (0.51%) 
Colon Adenoma * 1  0/191 (0.00%)  1/195 (0.51%) 
Colon Cancer * 1  0/191 (0.00%)  1/195 (0.51%) 
Desmoid Tumour * 1  0/191 (0.00%)  1/195 (0.51%) 
Gastrointestinal Carcinoma * 1  0/191 (0.00%)  1/195 (0.51%) 
Histiocytic Sarcoma * 1  0/191 (0.00%)  1/195 (0.51%) 
Intraductal Papillary Mucinous Neoplasm * 1  0/191 (0.00%)  1/195 (0.51%) 
Leukaemia * 1  0/191 (0.00%)  1/195 (0.51%) 
Myelodysplastic Syndrome * 1  0/191 (0.00%)  1/195 (0.51%) 
Squamous Cell Carcinoma * 1  1/191 (0.52%)  1/195 (0.51%) 
Squamous Cell Carcinoma of Lung * 1  0/191 (0.00%)  1/195 (0.51%) 
Tumour Flare * 1  0/191 (0.00%)  1/195 (0.51%) 
Metastatic Squamous Cell Carcinoma * 1  1/191 (0.52%)  0/195 (0.00%) 
Tumour Pain * 1  1/191 (0.52%)  0/195 (0.00%) 
Nervous system disorders     
Seizure * 1  0/191 (0.00%)  3/195 (1.54%) 
Cerebrovascular Accident * 1  0/191 (0.00%)  2/195 (1.03%) 
Transient Ischaemic Attack * 1  0/191 (0.00%)  2/195 (1.03%) 
Cerebral Haemorrhage * 1  0/191 (0.00%)  1/195 (0.51%) 
Dizziness * 1  0/191 (0.00%)  1/195 (0.51%) 
Encephalopathy * 1  0/191 (0.00%)  1/195 (0.51%) 
Sciatica * 1  0/191 (0.00%)  1/195 (0.51%) 
Syncope * 1  0/191 (0.00%)  1/195 (0.51%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy * 1  0/191 (0.00%)  1/195 (0.51%) 
Psychiatric disorders     
Mental Status Changes * 1  0/191 (0.00%)  3/195 (1.54%) 
Depression * 1  0/191 (0.00%)  1/195 (0.51%) 
Hallucination, Visual * 1  0/191 (0.00%)  1/195 (0.51%) 
Mania * 1  0/191 (0.00%)  1/195 (0.51%) 
Psychotic Disorder * 1  0/191 (0.00%)  1/195 (0.51%) 
Confusional State * 1  1/191 (0.52%)  0/195 (0.00%) 
Major Depression * 1  1/191 (0.52%)  0/195 (0.00%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  2/191 (1.05%)  4/195 (2.05%) 
Haematuria * 1  0/191 (0.00%)  2/195 (1.03%) 
Urinary Retention * 1  0/191 (0.00%)  2/195 (1.03%) 
Calculus Bladder * 1  0/191 (0.00%)  1/195 (0.51%) 
Hydronephrosis * 1  0/191 (0.00%)  1/195 (0.51%) 
Ureterolithiasis * 1  0/191 (0.00%)  1/195 (0.51%) 
Renal Failure * 1  1/191 (0.52%)  0/195 (0.00%) 
Renal Impairment * 1  1/191 (0.52%)  0/195 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute Respiratory Failure * 1  0/191 (0.00%)  4/195 (2.05%) 
Cough * 1  0/191 (0.00%)  3/195 (1.54%) 
Dyspnoea * 1  1/191 (0.52%)  3/195 (1.54%) 
Hypoxia * 1  0/191 (0.00%)  2/195 (1.03%) 
Pneumonia Aspiration * 1  0/191 (0.00%)  2/195 (1.03%) 
Asthma * 1  0/191 (0.00%)  1/195 (0.51%) 
Bronchopneumopathy * 1  0/191 (0.00%)  1/195 (0.51%) 
Chronic Obstructive Pulmonary Disease * 1  0/191 (0.00%)  1/195 (0.51%) 
Epistaxis * 1  1/191 (0.52%)  1/195 (0.51%) 
Lung Infiltration * 1  0/191 (0.00%)  1/195 (0.51%) 
Pleural Effusion * 1  0/191 (0.00%)  1/195 (0.51%) 
Haemoptysis * 1  1/191 (0.52%)  0/195 (0.00%) 
Pneumonitis * 1  1/191 (0.52%)  0/195 (0.00%) 
Pulmonary Embolism * 1  1/191 (0.52%)  0/195 (0.00%) 
Pulmonary Mass * 1  1/191 (0.52%)  0/195 (0.00%) 
Respiratory Tract Inflammation * 1  1/191 (0.52%)  0/195 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema * 1  0/191 (0.00%)  1/195 (0.51%) 
Pyoderma Gangrenosum * 1  0/191 (0.00%)  1/195 (0.51%) 
Vascular disorders     
Hypertension * 1  0/191 (0.00%)  2/195 (1.03%) 
Aneurysm * 1  0/191 (0.00%)  1/195 (0.51%) 
Deep Vein Thrombosis * 1  1/191 (0.52%)  0/195 (0.00%) 
1
Term from vocabulary, MeDRA 21.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ofatumumab (Arm A) Ibrutinib (Arm B)
Affected / at Risk (%) Affected / at Risk (%)
Total   185/191 (96.86%)   194/195 (99.49%) 
Blood and lymphatic system disorders     
Anaemia * 1  32/191 (16.75%)  62/195 (31.79%) 
Neutropenia * 1  25/191 (13.09%)  60/195 (30.77%) 
Increased Tendency to Bruise * 1  4/191 (2.09%)  45/195 (23.08%) 
Thrombocytopenia * 1  22/191 (11.52%)  45/195 (23.08%) 
Lymphocytosis * 1  5/191 (2.62%)  10/195 (5.13%) 
Cardiac disorders     
Atrial Fibrillation * 1  0/191 (0.00%)  19/195 (9.74%) 
Eye disorders     
Dry Eye * 1  10/191 (5.24%)  33/195 (16.92%) 
Vision Blurred * 1  6/191 (3.14%)  30/195 (15.38%) 
Lacrimation Increased * 1  5/191 (2.62%)  27/195 (13.85%) 
Cataract * 1  2/191 (1.05%)  26/195 (13.33%) 
Visual Acuity Reduced * 1  1/191 (0.52%)  19/195 (9.74%) 
Eye Irritation * 1  3/191 (1.57%)  17/195 (8.72%) 
Eye Pain * 1  5/191 (2.62%)  15/195 (7.69%) 
Photophobia * 1  4/191 (2.09%)  14/195 (7.18%) 
Vitreous Floaters * 1  3/191 (1.57%)  14/195 (7.18%) 
Gastrointestinal disorders     
Diarrhoea * 1  33/191 (17.28%)  120/195 (61.54%) 
Nausea * 1  38/191 (19.90%)  69/195 (35.38%) 
Constipation * 1  19/191 (9.95%)  45/195 (23.08%) 
Vomiting * 1  11/191 (5.76%)  39/195 (20.00%) 
Abdominal Pain * 1  19/191 (9.95%)  30/195 (15.38%) 
Stomatitis * 1  5/191 (2.62%)  30/195 (15.38%) 
Dyspepsia * 1  6/191 (3.14%)  22/195 (11.28%) 
Gastrooesophageal Reflux Disease * 1  3/191 (1.57%)  21/195 (10.77%) 
Dry Mouth * 1  1/191 (0.52%)  19/195 (9.74%) 
Abdominal Pain Upper * 1  3/191 (1.57%)  16/195 (8.21%) 
Flatulence * 1  2/191 (1.05%)  10/195 (5.13%) 
Haemorrhoids * 1  3/191 (1.57%)  10/195 (5.13%) 
General disorders     
Fatigue * 1  57/191 (29.84%)  82/195 (42.05%) 
Pyrexia * 1  27/191 (14.14%)  66/195 (33.85%) 
Oedema Peripheral * 1  16/191 (8.38%)  46/195 (23.59%) 
Asthenia * 1  8/191 (4.19%)  22/195 (11.28%) 
Chills * 1  6/191 (3.14%)  16/195 (8.21%) 
Influenza Like Illness * 1  5/191 (2.62%)  16/195 (8.21%) 
Malaise * 1  1/191 (0.52%)  10/195 (5.13%) 
Infections and infestations     
Upper Respiratory Tract Infection * 1  17/191 (8.90%)  77/195 (39.49%) 
Sinusitis * 1  12/191 (6.28%)  50/195 (25.64%) 
Urinary Tract Infection * 1  10/191 (5.24%)  46/195 (23.59%) 
Bronchitis * 1  2/191 (1.05%)  28/195 (14.36%) 
Nasopharyngitis * 1  7/191 (3.66%)  22/195 (11.28%) 
Conjunctivitis * 1  2/191 (1.05%)  21/195 (10.77%) 
Pneumonia * 1  3/191 (1.57%)  21/195 (10.77%) 
Cellulitis * 1  3/191 (1.57%)  15/195 (7.69%) 
Lower Respiratory Tract Infection * 1  0/191 (0.00%)  15/195 (7.69%) 
Herpes Zoster * 1  3/191 (1.57%)  14/195 (7.18%) 
Ear Infection * 1  2/191 (1.05%)  13/195 (6.67%) 
Folliculitis * 1  0/191 (0.00%)  10/195 (5.13%) 
Injury, poisoning and procedural complications     
Contusion * 1  6/191 (3.14%)  38/195 (19.49%) 
Fall * 1  1/191 (0.52%)  18/195 (9.23%) 
Traumatic Haematoma * 1  0/191 (0.00%)  12/195 (6.15%) 
Infusion Related Reaction * 1  64/191 (33.51%)  0/195 (0.00%) 
Investigations     
Weight Decreased * 1  11/191 (5.76%)  25/195 (12.82%) 
Blood Creatinine Increased * 1  0/191 (0.00%)  12/195 (6.15%) 
Platelet Count Decreased * 1  0/191 (0.00%)  11/195 (5.64%) 
Weight Increased * 1  0/191 (0.00%)  11/195 (5.64%) 
Metabolism and nutrition disorders     
Decreased Appetite * 1  16/191 (8.38%)  32/195 (16.41%) 
Hyperuricaemia * 1  4/191 (2.09%)  22/195 (11.28%) 
Hypokalaemia * 1  5/191 (2.62%)  22/195 (11.28%) 
Hyperglycaemia * 1  6/191 (3.14%)  16/195 (8.21%) 
Hyponatraemia * 1  3/191 (1.57%)  12/195 (6.15%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  14/191 (7.33%)  53/195 (27.18%) 
Muscle Spasms * 1  16/191 (8.38%)  46/195 (23.59%) 
Back Pain * 1  14/191 (7.33%)  39/195 (20.00%) 
Pain in Extremity * 1  9/191 (4.71%)  29/195 (14.87%) 
Myalgia * 1  7/191 (3.66%)  24/195 (12.31%) 
Musculoskeletal Pain * 1  9/191 (4.71%)  20/195 (10.26%) 
Bone Pain * 1  3/191 (1.57%)  10/195 (5.13%) 
Muscular Weakness * 1  3/191 (1.57%)  10/195 (5.13%) 
Neck Pain * 1  0/191 (0.00%)  10/195 (5.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal Cell Carcinoma * 1  2/191 (1.05%)  18/195 (9.23%) 
Squamous Cell Carcinoma * 1  2/191 (1.05%)  13/195 (6.67%) 
Nervous system disorders     
Headache * 1  12/191 (6.28%)  41/195 (21.03%) 
Dizziness * 1  10/191 (5.24%)  33/195 (16.92%) 
Peripheral Sensory Neuropathy * 1  26/191 (13.61%)  22/195 (11.28%) 
Paraesthesia * 1  10/191 (5.24%)  14/195 (7.18%) 
Psychiatric disorders     
Anxiety * 1  9/191 (4.71%)  18/195 (9.23%) 
Depression * 1  3/191 (1.57%)  17/195 (8.72%) 
Insomnia * 1  16/191 (8.38%)  17/195 (8.72%) 
Confusional State * 1  4/191 (2.09%)  11/195 (5.64%) 
Renal and urinary disorders     
Pollakiuria * 1  3/191 (1.57%)  19/195 (9.74%) 
Dysuria * 1  1/191 (0.52%)  12/195 (6.15%) 
Haematuria * 1  2/191 (1.05%)  12/195 (6.15%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  43/191 (22.51%)  78/195 (40.00%) 
Oropharyngeal pain * 1  9/191 (4.71%)  33/195 (16.92%) 
Dyspnoea * 1  18/191 (9.42%)  32/195 (16.41%) 
Epistaxis * 1  5/191 (2.62%)  30/195 (15.38%) 
Rhinorrhoea * 1  6/191 (3.14%)  19/195 (9.74%) 
Nasal Congestion * 1  6/191 (3.14%)  17/195 (8.72%) 
Dyspnoea Exertional * 1  4/191 (2.09%)  14/195 (7.18%) 
Productive Cough * 1  5/191 (2.62%)  14/195 (7.18%) 
Dysphonia * 1  0/191 (0.00%)  10/195 (5.13%) 
Skin and subcutaneous tissue disorders     
Petechiae * 1  2/191 (1.05%)  28/195 (14.36%) 
Rash Maculo-Papular * 1  7/191 (3.66%)  26/195 (13.33%) 
Night Sweats * 1  23/191 (12.04%)  24/195 (12.31%) 
Skin Lesion * 1  5/191 (2.62%)  24/195 (12.31%) 
Rash Erythematous * 1  9/191 (4.71%)  20/195 (10.26%) 
Pruritus * 1  18/191 (9.42%)  19/195 (9.74%) 
Rash * 1  7/191 (3.66%)  19/195 (9.74%) 
Dry Skin * 1  3/191 (1.57%)  18/195 (9.23%) 
Actinic Keratosis * 1  5/191 (2.62%)  16/195 (8.21%) 
Ecchymosis * 1  0/191 (0.00%)  12/195 (6.15%) 
Onychoclasis * 1  0/191 (0.00%)  12/195 (6.15%) 
Blood Blister * 1  1/191 (0.52%)  10/195 (5.13%) 
Skin Ulcer * 1  0/191 (0.00%)  10/195 (5.13%) 
Vascular disorders     
Hypertension * 1  4/191 (2.09%)  40/195 (20.51%) 
1
Term from vocabulary, MeDRA 21.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anita Szoke
Organization: Pharmacyclics, LLC
Phone: (669) 215-7235
EMail: aszoke@pcyc.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT01578707    
Other Study ID Numbers: PCYC-1112-CA
2012-000694-23 ( EudraCT Number )
First Submitted: April 11, 2012
First Posted: April 17, 2012
Results First Submitted: June 23, 2015
Results First Posted: October 12, 2015
Last Update Posted: December 18, 2019