Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

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ClinicalTrials.gov Identifier: NCT01325701

Recruitment Status : Completed

First Posted : March 30, 2011

Results First Posted : February 16, 2017

Last Update Posted : March 31, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Pharmacyclics LLC.

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Diffuse Large Cell B-lymphoma
Intervention	Drug: ibrutinib
Enrollment	78

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 78 subjects were enrolled: 70 were treated with PCI-32765 (ibrutinib) 560 mg daily, and 8 were treated with ibrutinib 840mg daily. All subjects received at least 1 dose of study drug.


Arm/Group Title	PCI-32765: 560 mg	PCI-32765: 840 mg
Arm/Group Description	Treatment Group 1: Subjects receive...	Treatment Group 2: Subjects receive...
Arm/Group Description	Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.	Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
Period Title: Overall Study
Started	70	8
Completed	49	5
Not Completed	21	3
Reason Not Completed
Adverse Event	12	0
Protocol Violation	1	0
Physician Decision	2	2
Withdrawal by Subject	2	1
Rollerover Extension Study	4	0

Baseline Characteristics

Arm/Group Title		PCI-32765: 560 mg	PCI-32765: 840 mg	Total
Arm/Group Description		Treatment Group 1: Subjects receive...	Treatment Group 2: Subjects receive...	Total of all reporting groups
Arm/Group Description		Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.	Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.	Total of all reporting groups
Overall Number of Baseline Participants		70	8	78
Baseline Analysis Population Description		...
Baseline Analysis Population Description		A total of 78 subjects were enrolled: 70 in PCI-32765: 560 mg , and 8 in PCI-32765: 840 mg . All subjects received at least 1 dose of study drug.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	70 participants	8 participants	78 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	38 54.3%	4 50.0%	42 53.8%
	>=65 years	32 45.7%	4 50.0%	36 46.2%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	70 participants	8 participants	78 participants
		62.5 (13.40)	64.4 (13.96)	62.7 (13.38)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	70 participants	8 participants	78 participants
	Female	20 28.6%	2 25.0%	22 28.2%
	Male	50 71.4%	6 75.0%	56 71.8%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	70 participants	8 participants	78 participants
United States		70	8	78

Outcome Measures

1.Primary Outcome


Title	Percentage of Patients With an Overall Response to Study Drug
Description	The primary endpoint of the study was overall response rate (ORR), def...
Description	The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator.
Time Frame	The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	PCI-32765: 560 mg	PCI-32765: 840 mg
Arm/Group Description:	Treatment Group 1: Subjects receive...	Treatment Group 2: Subjects receive...
Arm/Group Description:	Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.	Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
Overall Number of Participants Analyzed	70	8
Measure Type: Number Unit of Measure: percentage of participants
	24.3	12.5

2.Secondary Outcome


Title	Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Description	Participants will be followed until progression of the disease or star...
Description	Participants will be followed until progression of the disease or start of another anticancer treatment. The clinical database captured all AEs from baseline through end of treatment. Treatment Emergent AEs were collected pre-dose, at the beginning of each cycle and 30 days post last dose of study drug, unless related to study drug.
Time Frame	Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	PCI-32765: 560 mg	PCI-32765: 840 mg
Arm/Group Description:	Treatment Group 1: Subjects receive...	Treatment Group 2: Subjects receive...
Arm/Group Description:	Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.	Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
Overall Number of Participants Analyzed	70	8
Measure Type: Number Unit of Measure: participants
	70	8

3.Secondary Outcome


Title	Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765
Description	Treatment Group 1 PK collection schedule: ...
Description	Treatment Group 1 PK collection schedule: Cycle 1 Day 1: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 8: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Treatment Group 2 PK collection schedule: Cycle 1 Day 8: Pre-dose, 1, 2, 4 and 7 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Cycle 3 Day 1: Pre-dose, 1, 2, and 4 hours post-dose
Time Frame	Performed during the first month of receiving study drug.

Outcome Measure Data

Analysis Population Description

PK samples were collected in all participants (n=70 and 8 in PCI-32765: 560 mg and 840 mg, respectively). Of these, 59 participants in PCI-32765: 560 mg and 7 in PCI-32765: 840 mg on Cycle 1 Day 8 were evaluable for PK.


Arm/Group Title	PCI-32765: 560 mg	PCI-32765: 840 mg
Arm/Group Description:	Treatment Group 1: Subjects receive...	Treatment Group 2: Subjects receive...
Arm/Group Description:	Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis	Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
Overall Number of Participants Analyzed	59	7
Mean (Standard Deviation) Unit of Measure: ng*h/mL
PCI-32765 - Day 8	1285 (971)	1337 (1556)
PCI-45227 (Metabolite)- Day 8	1485 (948)	1671 (1147)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	PCI-32765: 560 mg	PCI-32765: 840 mg
Arm/Group Description	Treatment Group 1: Subjects receive...	Treatment Group 2: Subjects receive...
Arm/Group Description	Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.	Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
All-Cause Mortality
	PCI-32765: 560 mg	PCI-32765: 840 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	PCI-32765: 560 mg	PCI-32765: 840 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	40/70 (57.14%)	3/8 (37.50%)
Blood and lymphatic system disorders
Febrile neutropenia ^* 1	1/70 (1.43%)	1/8 (12.50%)
Splenic lesion ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cardiac disorders
Atrial fibrillation ^* 1	2/70 (2.86%)	0/8 (0.00%)
Cardiac arrest ^* 1	1/70 (1.43%)	0/8 (0.00%)
Myocardial infarction ^* 1	1/70 (1.43%)	0/8 (0.00%)
Endocrine disorders
Hypercalcaemia of malignancy ^* 1	0/70 (0.00%)	1/8 (12.50%)
Gastrointestinal disorders
Nausea ^* 1	3/70 (4.29%)	0/8 (0.00%)
Vomiting ^* 1	2/70 (2.86%)	0/8 (0.00%)
Abdominal pain ^* 1	1/70 (1.43%)	0/8 (0.00%)
Diarrhoea ^* 1	1/70 (1.43%)	0/8 (0.00%)
Melaena ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pancreatitis ^* 1	0/70 (0.00%)	1/8 (12.50%)
General disorders
Localised oedema ^* 1	2/70 (2.86%)	0/8 (0.00%)
Pyrexia ^* 1	2/70 (2.86%)	0/8 (0.00%)
Fatigue ^* 1	1/70 (1.43%)	0/8 (0.00%)
Non-cardiac chest pain ^* 1	0/70 (0.00%)	1/8 (12.50%)
Oedema peripheral ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hepatobiliary disorders
Hyperbilirubinaemia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Infections and infestations
Pneumonia ^* 1	7/70 (10.00%)	1/8 (12.50%)
Sepsis ^* 1	3/70 (4.29%)	0/8 (0.00%)
Cytomegalovirus infection ^* 1	1/70 (1.43%)	0/8 (0.00%)
Enterobacter sepsis ^* 1	0/70 (0.00%)	1/8 (12.50%)
Pseudomonal sepsis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Sinusitis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Staphylococcal sepsis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Urinary tract infection ^* 1	1/70 (1.43%)	0/8 (0.00%)
Investigations
Platelet count decreased ^* 1	1/70 (1.43%)	0/8 (0.00%)
Metabolism and nutrition disorders
Dehydration ^* 1	0/70 (0.00%)	2/8 (25.00%)
Hyperuricaemia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hyponatraemia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Musculoskeletal and connective tissue disorders
Neck mass ^* 1	2/70 (2.86%)	0/8 (0.00%)
Chest wall mass ^* 1	1/70 (1.43%)	0/8 (0.00%)
Muscular weakness ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pain in extremity ^* 1	1/70 (1.43%)	0/8 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma ^* 1	5/70 (7.14%)	2/8 (25.00%)
Nervous system disorders
Brain mass ^* 1	1/70 (1.43%)	0/8 (0.00%)
Intraventricular haemorrhage ^* 1	1/70 (1.43%)	0/8 (0.00%)
Renal and urinary disorders
Renal failure ^* 1	2/70 (2.86%)	0/8 (0.00%)
Renal failure acute ^* 1	2/70 (2.86%)	0/8 (0.00%)
Nephrolithiasis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Urinary retention ^* 1	1/70 (1.43%)	0/8 (0.00%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure ^* 1	4/70 (5.71%)	0/8 (0.00%)
Pleural effusion ^* 1	2/70 (2.86%)	0/8 (0.00%)
Bronchial obstruction ^* 1	1/70 (1.43%)	0/8 (0.00%)
Dyspnoea ^* 1	1/70 (1.43%)	0/8 (0.00%)
Dyspnoea exertional ^* 1	1/70 (1.43%)	0/8 (0.00%)
Laryngeal obstruction ^* 1	1/70 (1.43%)	0/8 (0.00%)
Respiratory depression ^* 1	1/70 (1.43%)	0/8 (0.00%)
Vascular disorders
Hypotension ^* 1	0/70 (0.00%)	1/8 (12.50%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA version 17.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	PCI-32765: 560 mg	PCI-32765: 840 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	70/70 (100.00%)	8/8 (100.00%)
Blood and lymphatic system disorders
Anaemia ^* 1	20/70 (28.57%)	1/8 (12.50%)
Thrombocytopenia ^* 1	15/70 (21.43%)	1/8 (12.50%)
Neutropenia ^* 1	7/70 (10.00%)	1/8 (12.50%)
Leukopenia ^* 1	3/70 (4.29%)	0/8 (0.00%)
Febrile neutropenia ^* 1	1/70 (1.43%)	1/8 (12.50%)
Lymph node pain ^* 1	2/70 (2.86%)	0/8 (0.00%)
Haemorrhagic diathesis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Increased tendency to bruise ^* 1	1/70 (1.43%)	0/8 (0.00%)
Lymphadenopathy ^* 1	1/70 (1.43%)	0/8 (0.00%)
Lymphopenia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Splenic lesion ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cardiac disorders
Bradycardia ^* 1	2/70 (2.86%)	1/8 (12.50%)
Atrial fibrillation ^* 1	2/70 (2.86%)	0/8 (0.00%)
Sinus tachycardia ^* 1	2/70 (2.86%)	0/8 (0.00%)
Cardiac arrest ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cardiomegaly ^* 1	1/70 (1.43%)	0/8 (0.00%)
Myocardial infarction ^* 1	1/70 (1.43%)	0/8 (0.00%)
Palpitations ^* 1	1/70 (1.43%)	0/8 (0.00%)
Tachycardia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Ear and labyrinth disorders
Tinnitus ^* 1	2/70 (2.86%)	0/8 (0.00%)
Deafness unilateral ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hearing impaired ^* 1	1/70 (1.43%)	0/8 (0.00%)
Vertigo ^* 1	1/70 (1.43%)	0/8 (0.00%)
Endocrine disorders
Hypercalcaemia of malignancy ^* 1	0/70 (0.00%)	1/8 (12.50%)
Hypothyroidism ^* 1	1/70 (1.43%)	0/8 (0.00%)
Inappropriate antidiuretic hormone secretion ^* 1	1/70 (1.43%)	0/8 (0.00%)
Eye disorders
Dry eye ^* 1	3/70 (4.29%)	0/8 (0.00%)
Eye pain ^* 1	2/70 (2.86%)	0/8 (0.00%)
Vision blurred ^* 1	2/70 (2.86%)	0/8 (0.00%)
Conjunctival haemorrhage ^* 1	1/70 (1.43%)	0/8 (0.00%)
Eye discharge ^* 1	1/70 (1.43%)	0/8 (0.00%)
Eye swelling ^* 1	1/70 (1.43%)	0/8 (0.00%)
Glaucoma ^* 1	1/70 (1.43%)	0/8 (0.00%)
Lacrimation increased ^* 1	1/70 (1.43%)	0/8 (0.00%)
Ocular hyperaemia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Visual impairment ^* 1	1/70 (1.43%)	0/8 (0.00%)
Gastrointestinal disorders
Diarrhoea ^* 1	28/70 (40.00%)	3/8 (37.50%)
Nausea ^* 1	24/70 (34.29%)	4/8 (50.00%)
Constipation ^* 1	11/70 (15.71%)	1/8 (12.50%)
Vomiting ^* 1	9/70 (12.86%)	0/8 (0.00%)
Abdominal pain ^* 1	8/70 (11.43%)	0/8 (0.00%)
Dyspepsia ^* 1	8/70 (11.43%)	0/8 (0.00%)
Stomatitis ^* 1	7/70 (10.00%)	0/8 (0.00%)
Abdominal distension ^* 1	5/70 (7.14%)	0/8 (0.00%)
Dry mouth ^* 1	4/70 (5.71%)	0/8 (0.00%)
Flatulence ^* 1	4/70 (5.71%)	0/8 (0.00%)
Ascites ^* 1	2/70 (2.86%)	0/8 (0.00%)
Gastrooesophageal reflux disease ^* 1	2/70 (2.86%)	0/8 (0.00%)
Abdominal discomfort ^* 1	1/70 (1.43%)	0/8 (0.00%)
Abdominal mass ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cheilitis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Dysphagia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Frequent bowel movements ^* 1	1/70 (1.43%)	0/8 (0.00%)
Gingivitis ulcerative ^* 1	1/70 (1.43%)	0/8 (0.00%)
Melaena ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pancreatitis ^* 1	0/70 (0.00%)	1/8 (12.50%)
Salivary gland enlargement ^* 1	1/70 (1.43%)	0/8 (0.00%)
Salivary gland pain ^* 1	1/70 (1.43%)	0/8 (0.00%)
Sensitivity of teeth ^* 1	1/70 (1.43%)	0/8 (0.00%)
General disorders
Fatigue ^* 1	30/70 (42.86%)	0/8 (0.00%)
Pyrexia ^* 1	14/70 (20.00%)	1/8 (12.50%)
Oedema peripheral ^* 1	12/70 (17.14%)	1/8 (12.50%)
Chills ^* 1	5/70 (7.14%)	1/8 (12.50%)
Pain ^* 1	5/70 (7.14%)	1/8 (12.50%)
Asthenia ^* 1	4/70 (5.71%)	0/8 (0.00%)
Local swelling ^* 1	4/70 (5.71%)	0/8 (0.00%)
Localised oedema ^* 1	3/70 (4.29%)	0/8 (0.00%)
Face oedema ^* 1	2/70 (2.86%)	0/8 (0.00%)
Malaise ^* 1	1/70 (1.43%)	1/8 (12.50%)
Non-cardiac chest pain ^* 1	0/70 (0.00%)	2/8 (25.00%)
Catheter site erythema ^* 1	1/70 (1.43%)	0/8 (0.00%)
Chest discomfort ^* 1	1/70 (1.43%)	0/8 (0.00%)
Chest pain ^* 1	1/70 (1.43%)	0/8 (0.00%)
Gait disturbance ^* 1	1/70 (1.43%)	0/8 (0.00%)
Oedema ^* 1	1/70 (1.43%)	0/8 (0.00%)
Suprapubic pain ^* 1	1/70 (1.43%)	0/8 (0.00%)
Tenderness ^* 1	1/70 (1.43%)	0/8 (0.00%)
Vessel puncture site haematoma ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hepatobiliary disorders
Hepatic function abnormal ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hyperbilirubinaemia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Immune system disorders
Hypogammaglobulinaemia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Infections and infestations
Pneumonia ^* 1	8/70 (11.43%)	1/8 (12.50%)
Urinary tract infection ^* 1	5/70 (7.14%)	1/8 (12.50%)
Upper respiratory tract infection ^* 1	4/70 (5.71%)	0/8 (0.00%)
Sepsis ^* 1	3/70 (4.29%)	0/8 (0.00%)
Candida infection ^* 1	2/70 (2.86%)	0/8 (0.00%)
Herpes zoster ^* 1	2/70 (2.86%)	0/8 (0.00%)
Sinusitis ^* 1	2/70 (2.86%)	0/8 (0.00%)
Skin infection ^* 1	1/70 (1.43%)	1/8 (12.50%)
Conjunctivitis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cystitis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cytomegalovirus infection ^* 1	1/70 (1.43%)	0/8 (0.00%)
Enterobacter sepsis ^* 1	0/70 (0.00%)	1/8 (12.50%)
Furuncle ^* 1	1/70 (1.43%)	0/8 (0.00%)
Herpes virus infection ^* 1	1/70 (1.43%)	0/8 (0.00%)
Laryngitis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Nail infection ^* 1	1/70 (1.43%)	0/8 (0.00%)
Nasopharyngitis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Paronychia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pseudomonal sepsis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Rhinovirus infection ^* 1	0/70 (0.00%)	1/8 (12.50%)
Staphylococcal sepsis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Injury, poisoning and procedural complications
Contusion ^* 1	5/70 (7.14%)	0/8 (0.00%)
Fall ^* 1	2/70 (2.86%)	0/8 (0.00%)
Arthropod bite ^* 1	1/70 (1.43%)	0/8 (0.00%)
Laceration ^* 1	1/70 (1.43%)	0/8 (0.00%)
Limb injury ^* 1	1/70 (1.43%)	0/8 (0.00%)
Mouth injury ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pneumothorax traumatic ^* 1	1/70 (1.43%)	0/8 (0.00%)
Thermal burn ^* 1	1/70 (1.43%)	0/8 (0.00%)
Toxicity to various agents ^* 1	1/70 (1.43%)	0/8 (0.00%)
Traumatic haematoma ^* 1	1/70 (1.43%)	0/8 (0.00%)
Urostomy complication ^* 1	1/70 (1.43%)	0/8 (0.00%)
Investigations
Platelet count decreased ^* 1	11/70 (15.71%)	1/8 (12.50%)
Alanine aminotransferase increased ^* 1	6/70 (8.57%)	3/8 (37.50%)
Aspartate aminotransferase increased ^* 1	7/70 (10.00%)	2/8 (25.00%)
Lymphocyte count decreased ^* 1	8/70 (11.43%)	0/8 (0.00%)
Blood bilirubin increased ^* 1	6/70 (8.57%)	1/8 (12.50%)
Blood alkaline phosphatase increased ^* 1	5/70 (7.14%)	1/8 (12.50%)
International normalised ratio increased ^* 1	6/70 (8.57%)	0/8 (0.00%)
White blood cell count decreased ^* 1	6/70 (8.57%)	0/8 (0.00%)
Blood creatinine increased ^* 1	5/70 (7.14%)	0/8 (0.00%)
Neutrophil count decreased ^* 1	4/70 (5.71%)	1/8 (12.50%)
Weight decreased ^* 1	4/70 (5.71%)	0/8 (0.00%)
Weight increased ^* 1	2/70 (2.86%)	1/8 (12.50%)
Activated partial thromboplastin time prolonged ^* 1	2/70 (2.86%)	0/8 (0.00%)
Amylase increased ^* 1	0/70 (0.00%)	1/8 (12.50%)
Blood uric acid increased ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cardiac murmur ^* 1	1/70 (1.43%)	0/8 (0.00%)
Gamma-glutamyltransferase increased ^* 1	1/70 (1.43%)	0/8 (0.00%)
Lipase increased ^* 1	0/70 (0.00%)	1/8 (12.50%)
Prothrombin time prolonged ^* 1	1/70 (1.43%)	0/8 (0.00%)
Transaminases increased ^* 1	1/70 (1.43%)	0/8 (0.00%)
Urine output decreased ^* 1	1/70 (1.43%)	0/8 (0.00%)
Metabolism and nutrition disorders
Hypomagnesaemia ^* 1	14/70 (20.00%)	1/8 (12.50%)
Hyperglycaemia ^* 1	13/70 (18.57%)	1/8 (12.50%)
Hypoalbuminaemia ^* 1	11/70 (15.71%)	2/8 (25.00%)
Hyponatraemia ^* 1	10/70 (14.29%)	1/8 (12.50%)
Decreased appetite ^* 1	9/70 (12.86%)	0/8 (0.00%)
Hypocalcaemia ^* 1	8/70 (11.43%)	1/8 (12.50%)
Hypokalaemia ^* 1	8/70 (11.43%)	1/8 (12.50%)
Dehydration ^* 1	5/70 (7.14%)	2/8 (25.00%)
Hypercalcaemia ^* 1	5/70 (7.14%)	0/8 (0.00%)
Hyperuricaemia ^* 1	4/70 (5.71%)	0/8 (0.00%)
Hypoglycaemia ^* 1	4/70 (5.71%)	0/8 (0.00%)
Hypernatraemia ^* 1	3/70 (4.29%)	0/8 (0.00%)
Hypophosphataemia ^* 1	2/70 (2.86%)	1/8 (12.50%)
Fluid overload ^* 1	2/70 (2.86%)	0/8 (0.00%)
Hyperkalaemia ^* 1	2/70 (2.86%)	0/8 (0.00%)
Hypermagnesaemia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hypertriglyceridaemia ^* 1	0/70 (0.00%)	1/8 (12.50%)
Hypophagia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Metabolic acidosis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	10/70 (14.29%)	0/8 (0.00%)
Myalgia ^* 1	10/70 (14.29%)	0/8 (0.00%)
Back pain ^* 1	7/70 (10.00%)	0/8 (0.00%)
Neck pain ^* 1	6/70 (8.57%)	0/8 (0.00%)
Pain in extremity ^* 1	4/70 (5.71%)	0/8 (0.00%)
Musculoskeletal pain ^* 1	3/70 (4.29%)	0/8 (0.00%)
Bone pain ^* 1	2/70 (2.86%)	0/8 (0.00%)
Muscle spasms ^* 1	2/70 (2.86%)	0/8 (0.00%)
Muscular weakness ^* 1	2/70 (2.86%)	0/8 (0.00%)
Musculoskeletal chest pain ^* 1	2/70 (2.86%)	0/8 (0.00%)
Neck mass ^* 1	2/70 (2.86%)	0/8 (0.00%)
Chest wall mass ^* 1	1/70 (1.43%)	0/8 (0.00%)
Foot deformity ^* 1	1/70 (1.43%)	0/8 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma ^* 1	5/70 (7.14%)	2/8 (25.00%)
Squamous cell carcinoma ^* 1	1/70 (1.43%)	0/8 (0.00%)
Nervous system disorders
Dizziness ^* 1	7/70 (10.00%)	2/8 (25.00%)
Headache ^* 1	7/70 (10.00%)	0/8 (0.00%)
Dysgeusia ^* 1	2/70 (2.86%)	0/8 (0.00%)
Tremor ^* 1	2/70 (2.86%)	0/8 (0.00%)
Brain mass ^* 1	1/70 (1.43%)	0/8 (0.00%)
Cognitive disorder ^* 1	1/70 (1.43%)	0/8 (0.00%)
Disturbance in attention ^* 1	1/70 (1.43%)	0/8 (0.00%)
Dizziness postural ^* 1	1/70 (1.43%)	0/8 (0.00%)
Intraventricular haemorrhage ^* 1	1/70 (1.43%)	0/8 (0.00%)
Lethargy ^* 1	1/70 (1.43%)	0/8 (0.00%)
Memory impairment ^* 1	1/70 (1.43%)	0/8 (0.00%)
Paraesthesia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Peripheral sensorimotor neuropathy ^* 1	1/70 (1.43%)	0/8 (0.00%)
Peripheral sensory neuropathy ^* 1	1/70 (1.43%)	0/8 (0.00%)
Sinus headache ^* 1	0/70 (0.00%)	1/8 (12.50%)
Somnolence ^* 1	1/70 (1.43%)	0/8 (0.00%)
Syncope ^* 1	1/70 (1.43%)	0/8 (0.00%)
Psychiatric disorders
Insomnia ^* 1	7/70 (10.00%)	3/8 (37.50%)
Anxiety ^* 1	5/70 (7.14%)	0/8 (0.00%)
Anxiety disorder due to a general medical condition ^* 1	1/70 (1.43%)	0/8 (0.00%)
Confusional state ^* 1	1/70 (1.43%)	0/8 (0.00%)
Delirium ^* 1	0/70 (0.00%)	1/8 (12.50%)
Depression ^* 1	0/70 (0.00%)	1/8 (12.50%)
Hallucination ^* 1	1/70 (1.43%)	0/8 (0.00%)
Mental status changes ^* 1	1/70 (1.43%)	0/8 (0.00%)
Renal and urinary disorders
Oliguria ^* 1	2/70 (2.86%)	0/8 (0.00%)
Renal failure ^* 1	2/70 (2.86%)	0/8 (0.00%)
Renal failure acute ^* 1	2/70 (2.86%)	0/8 (0.00%)
Haematuria ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hydronephrosis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Nephrolithiasis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Nocturia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pollakiuria ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pyuria ^* 1	1/70 (1.43%)	0/8 (0.00%)
Urinary retention ^* 1	1/70 (1.43%)	0/8 (0.00%)
Reproductive system and breast disorders
Penile oedema ^* 1	1/70 (1.43%)	0/8 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	14/70 (20.00%)	0/8 (0.00%)
Dyspnoea ^* 1	10/70 (14.29%)	0/8 (0.00%)
Pleural effusion ^* 1	5/70 (7.14%)	0/8 (0.00%)
Oropharyngeal pain ^* 1	4/70 (5.71%)	0/8 (0.00%)
Respiratory failure ^* 1	4/70 (5.71%)	0/8 (0.00%)
Epistaxis ^* 1	3/70 (4.29%)	0/8 (0.00%)
Nasal congestion ^* 1	2/70 (2.86%)	1/8 (12.50%)
Upper-airway cough syndrome ^* 1	3/70 (4.29%)	0/8 (0.00%)
Dyspnoea exertional ^* 1	2/70 (2.86%)	0/8 (0.00%)
Rhinorrhoea ^* 1	2/70 (2.86%)	0/8 (0.00%)
Bronchial obstruction ^* 1	1/70 (1.43%)	0/8 (0.00%)
Dysphonia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Hypoxia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Laryngeal obstruction ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pleuritic pain ^* 1	1/70 (1.43%)	0/8 (0.00%)
Pneumonitis ^* 1	1/70 (1.43%)	0/8 (0.00%)
Productive cough ^* 1	1/70 (1.43%)	0/8 (0.00%)
Respiratory depression ^* 1	1/70 (1.43%)	0/8 (0.00%)
Respiratory distress ^* 1	1/70 (1.43%)	0/8 (0.00%)
Rhinalgia ^* 1	1/70 (1.43%)	0/8 (0.00%)
Rhinitis allergic ^* 1	1/70 (1.43%)	0/8 (0.00%)
Sinus congestion ^* 1	1/70 (1.43%)	0/8 (0.00%)
Sneezing ^* 1	1/70 (1.43%)	0/8 (0.00%)
Tracheal inflammation ^* 1	1/70 (1.43%)	0/8 (0.00%)
Skin and subcutaneous tissue disorders
Rash maculo-papular ^* 1	6/70 (8.57%)	0/8 (0.00%)
Night sweats ^* 1	5/70 (7.14%)	0/8 (0.00%)
Alopecia ^* 1	3/70 (4.29%)	0/8 (0.00%)
Dry skin ^* 1	3/70 (4.29%)	0/8 (0.00%)
Pruritus ^* 1	3/70 (4.29%)	0/8 (0.00%)
Rash ^* 1	3/70 (4.29%)	0/8 (0.00%)
Ecchymosis ^* 1	2/70 (2.86%)	0/8 (0.00%)
Erythema ^* 1	2/70 (2.86%)	0/8 (0.00%)
Hyperhidrosis ^* 1	1/70 (1.43%)	1/8 (12.50%)
Rash macular ^* 1	2/70 (2.86%)	0/8 (0.00%)
Acne ^* 1	1/70 (1.43%)	0/8 (0.00%)
Acne cystic ^* 1	1/70 (1.43%)	0/8 (0.00%)
Decubitus ulcer ^* 1	1/70 (1.43%)	0/8 (0.00%)
Dermatitis acneiform ^* 1	1/70 (1.43%)	0/8 (0.00%)
Nail ridging ^* 1	1/70 (1.43%)	0/8 (0.00%)
Purpura ^* 1	1/70 (1.43%)	0/8 (0.00%)
Rash erythematous ^* 1	1/70 (1.43%)	0/8 (0.00%)
Rash pruritic ^* 1	1/70 (1.43%)	0/8 (0.00%)
Skin mass ^* 1	1/70 (1.43%)	0/8 (0.00%)
Swelling face ^* 1	1/70 (1.43%)	0/8 (0.00%)
Vascular disorders
Hypotension ^* 1	4/70 (5.71%)	1/8 (12.50%)
Jugular vein distension ^* 1	1/70 (1.43%)	0/8 (0.00%)
Orthostatic hypotension ^* 1	1/70 (1.43%)	0/8 (0.00%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA version 17.0

Limitations and Caveats

PCI-32765:840 mg:8 subjects were enrolled and followed through their 1st response assessment. Due to a lack of positive responses observed, enrollment was terminated for futility. Response rate should not be generalized due to small sample size.

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

Layout table for Results Point of Contact information

Name/Title:	Dr. Darrin Beaupre
Organization:	Pharmacyclics, Inc.
Phone:	855-427-8846
EMail:	medinfo@pcyc.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. doi: 10.1038/nm.3884. Epub 2015 Jul 20.

Layout table for additonal information

Responsible Party:	Pharmacyclics LLC.
ClinicalTrials.gov Identifier:	NCT01325701
Other Study ID Numbers:	PCYC-1106-CA PCI-32765 ( Other Identifier: Pharmacyclics )
First Submitted:	February 2, 2011
First Posted:	March 30, 2011
Results First Submitted:	June 30, 2016
Results First Posted:	February 16, 2017
Last Update Posted:	March 31, 2017

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