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

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ClinicalTrials.gov Identifier: NCT01578707

Recruitment Status : Completed

First Posted : April 17, 2012

Results First Posted : October 12, 2015

Last Update Posted : December 18, 2019

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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

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Ofatumumab (Arm A)	Ibrutinib (Arm B)
Arm/Group Description	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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

Baseline Characteristics

Arm/Group Title		Ofatumumab (Arm A)	Ibrutinib (Arm B)	Total
Arm/Group Description		An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...	Total of all reporting groups
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
Baseline Analysis Population Description		[Not Specified]
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%

Outcome Measures

1.Primary Outcome


Title	PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013
Description	The primary objective of this study was to evaluate the efficacy of ib...
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ofatumumab (Arm A)	Ibrutinib (Arm B)
Arm/Group Description:	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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.

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)
Description	Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, ...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ofatumumab (Arm A)	Ibrutinib (Arm B)
Arm/Group Description:	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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

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)
Description	OS analysis was conducted at the time of study closure, with no adjust...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ofatumumab (Arm A)	Ibrutinib (Arm B)
Arm/Group Description:	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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.

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
Description	Proportion of subjects with hemoglobin (HgB) increase >=20 g/L and ...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ofatumumab (Arm A)	Ibrutinib (Arm B)
Arm/Group Description:	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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
Description	Long-Term Progression Free Survival as assessed by the investigator wi...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ofatumumab (Arm A)	Ibrutinib (Arm B)
Arm/Group Description:	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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
Description	Overall response per the IWCLL 2008 criteria as assessed by Investigat...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ofatumumab (Arm A)	Ibrutinib (Arm B)
Arm/Group Description:	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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

Adverse Events

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)
Arm/Group Description	An anti-CD20 monoclonal antibody ...	A Bruton Tyrosine Kinase Inhibitor ...
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%)
Serious Adverse Events 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
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

Limitations and Caveats

[Not Specified]

More Information

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

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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):

Munir T, Brown JR, O'Brien S, Barrientos JC, Barr PM, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Kipps TJ, Moreno C, Montillo M, Burger JA, Byrd JC, Hillmen P, Dai S, Szoke A, Dean JP, Woyach JA. Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol. 2019 Dec;94(12):1353-1363. doi: 10.1002/ajh.25638. Epub 2019 Oct 13.

Coutre SE, Byrd JC, Hillmen P, Barrientos JC, Barr PM, Devereux S, Robak T, Kipps TJ, Schuh A, Moreno C, Furman RR, Burger JA, O'Dwyer M, Ghia P, Valentino R, Chang S, Dean JP, James DF, O'Brien SM. Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies. Blood Adv. 2019 Jun 25;3(12):1799-1807. doi: 10.1182/bloodadvances.2018028761.

Byrd JC, Hillmen P, O'Brien S, Barrientos JC, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Barr PM, Furman RR, Kipps TJ, Thornton P, Moreno C, Montillo M, Pagel JM, Burger JA, Woyach JA, Dai S, Vezan R, James DF, Brown JR. Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. Blood. 2019 May 9;133(19):2031-2042. doi: 10.1182/blood-2018-08-870238. Epub 2019 Mar 6.

O'Brien SM, Jaglowski S, Byrd JC, Bannerji R, Blum KA, Fox CP, Furman RR, Hillmen P, Kipps TJ, Montillo M, Sharman J, Suzuki S, James DF, Chu AD, Coutre SE. Prognostic Factors for Complete Response to Ibrutinib in Patients With Chronic Lymphocytic Leukemia: A Pooled Analysis of 2 Clinical Trials. JAMA Oncol. 2018 May 1;4(5):712-716. doi: 10.1001/jamaoncol.2017.5604.

Brown JR, Moslehi J, O'Brien S, Ghia P, Hillmen P, Cymbalista F, Shanafelt TD, Fraser G, Rule S, Kipps TJ, Coutre S, Dilhuydy MS, Cramer P, Tedeschi A, Jaeger U, Dreyling M, Byrd JC, Howes A, Todd M, Vermeulen J, James DF, Clow F, Styles L, Valentino R, Wildgust M, Mahler M, Burger JA. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica. 2017 Oct;102(10):1796-1805. doi: 10.3324/haematol.2017.171041. Epub 2017 Jul 27.

Barr PM, Brown JR, Hillmen P, O'Brien S, Barrientos JC, Reddy NM, Coutre S, Mulligan SP, Jaeger U, Furman RR, Cymbalista F, Montillo M, Dearden C, Robak T, Moreno C, Pagel JM, Burger JA, Suzuki S, Sukbuntherng J, Cole G, James DF, Byrd JC. Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL. Blood. 2017 May 11;129(19):2612-2615. doi: 10.1182/blood-2016-12-737346. Epub 2017 Apr 3.

Maddocks KJ, Ruppert AS, Lozanski G, Heerema NA, Zhao W, Abruzzo L, Lozanski A, Davis M, Gordon A, Smith LL, Mantel R, Jones JA, Flynn JM, Jaglowski SM, Andritsos LA, Awan F, Blum KA, Grever MR, Johnson AJ, Byrd JC, Woyach JA. Etiology of Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic Lymphocytic Leukemia. JAMA Oncol. 2015 Apr;1(1):80-7. doi: 10.1001/jamaoncol.2014.218.

Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, de Vos S, Gill D, Bloor A, Dearden C, Moreno C, Jones JJ, Chu AD, Fardis M, McGreivy J, Clow F, James DF, Hillmen P; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014 Jul 17;371(3):213-23. doi: 10.1056/NEJMoa1400376. Epub 2014 May 31.

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

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