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Ibrutinib (PCI-32765) in Waldenstrom's Macroglobulinemia

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: NCT01614821

Recruitment Status : Completed

First Posted : June 8, 2012

Results First Posted : January 21, 2020

Last Update Posted : January 21, 2020

Sponsor:

Information provided by (Responsible Party):

Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Waldenstrom's Macroglobulinemia
Intervention	Drug: PCI-32765
Enrollment	63

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Treatment Arm
Arm/Group Description	PCI-32765; ibrutinib ...
Arm/Group Description	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Period Title: Overall Study
Started	63
Completed	63
Not Completed	0

Baseline Characteristics

Arm/Group Title		Treatment Arm
Arm/Group Description		PCI-32765; ibrutinib ...
Arm/Group Description		PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Overall Number of Baseline Participants		63
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	63 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	32 50.8%
	>=65 years	31 49.2%
Age, Continuous Median (Standard Deviation) Unit of measure: Years
	Number Analyzed	63 participants
		63 (10.6)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	63 participants
	Female	15 23.8%
	Male	48 76.2%
Race and Ethnicity Not Collected ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	63 participants
United States		63

Outcome Measures

1.Primary Outcome


Title	Overall Response Rate
Description	To assess the overall response rate (>25% reduction in serum IgM fr...
Description	To assess the overall response rate (>25% reduction in serum IgM from baseline).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Arm
Arm/Group Description:	PCI-32765; ibrutinib ...
Arm/Group Description:	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants Unit of Measure: Participants
	57 90.5%

2.Secondary Outcome


Title	Safety and Tolerability of PCI-32765
Description	To assess the safety and tolerability of PCI-32765 in symptomatic WM p...
Description	To assess the safety and tolerability of PCI-32765 in symptomatic WM patients with relapsed/refractory disease. Grade > or = 2 Adverse Events determined to be associated with PCI-32765 and subsequent outcomes will constitute the safety profile of PCI-32765 in WM. Percent of participants who experienced at least 1 grade 2 or higher treatment emergent adverse event.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Arm
Arm/Group Description:	PCI-32765; ibrutinib ...
Arm/Group Description:	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants Unit of Measure: Participants
	62 98.4%

3.Secondary Outcome


Title	Determine Progression Free Survival
Description	To determine Progression Free Survival (PFS in symptomatic WM patients...
Description	To determine Progression Free Survival (PFS in symptomatic WM patients with relapsed/refractory disease. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. 40 participants were censored prior to disease progression.
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Arm
Arm/Group Description:	PCI-32765; ibrutinib ...
Arm/Group Description:	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Overall Number of Participants Analyzed	63
Median (Full Range) Unit of Measure: months
	39 (0 to 67)

4.Secondary Outcome


Title	To Determine Time to Next Therapy (TTNT) of PCI-32765 in Symptomatic WM Patients With Relapsed/Refractory Disease
Description	Time to Next Therapy is the duration of time from of starting ibrutini...
Description	Time to Next Therapy is the duration of time from of starting ibrutinib until next therapy. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. Participants had the option to continue ibrutinib commercially. 40 participants were censored while still on commercial ibrutinib therapy.
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Arm
Arm/Group Description:	PCI-32765; ibrutinib ...
Arm/Group Description:	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Overall Number of Participants Analyzed	63
Median (Full Range) Unit of Measure: months
	49 (1 to 67)

5.Secondary Outcome


Title	Major Response Rates
Description	To assess the major response rate (>50% reduction in serum IgM from...
Description	To assess the major response rate (>50% reduction in serum IgM from baseline)
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Arm
Arm/Group Description:	PCI-32765; ibrutinib ...
Arm/Group Description:	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants Unit of Measure: Participants
	49 77.8%

6.Secondary Outcome


Title	Very Good Partial Response Rate
Description	To assess the very good partial response rate (>90% reduction in se...
Description	To assess the very good partial response rate (>90% reduction in serum IgM from baseline)
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Arm
Arm/Group Description:	PCI-32765; ibrutinib ...
Arm/Group Description:	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants Unit of Measure: Participants
	17 27.0%

Adverse Events

Time Frame	Adverse events were collected from Cycle 1 Day 1 through 30 days after discontinuing protocol ibrutinib therapy, an average of 3 years.
Adverse Event Reporting Description	Grade 2 and above treatment emergent adverse events were collected.

Arm/Group Title	Treatment Arm
Arm/Group Description	PCI-32765; ibrutinib ...
Arm/Group Description	PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning
All-Cause Mortality
	Treatment Arm
	Affected / at Risk (%)
Total	1/63 (1.59%)
Serious Adverse Events Serious Adverse Events
	Treatment Arm
	Affected / at Risk (%)	# Events
Total	30/63 (47.62%)
Blood and lymphatic system disorders
Neutropenic Fever and Chills ^†	1/63 (1.59%)	1
Anemia ^†	2/63 (3.17%)	2
Cardiac disorders
Atrial Fibrillation ^†	2/63 (3.17%)	2
Pericarditis ^†	1/63 (1.59%)	1
General disorders
Fever and Tachycardia ^†	1/63 (1.59%)	1
Malaise ^†	1/63 (1.59%)	1
Fever ^†	3/63 (4.76%)	3
Hepatobiliary disorders
Cholecystitis ^†	1/63 (1.59%)	1
Infections and infestations
Flu ^†	1/63 (1.59%)	1
Cellulitis ^†	1/63 (1.59%)	1
Pneumonia ^†	11/63 (17.46%)	11
Endocarditis ^†	1/63 (1.59%)	1
Herpes Zoster ^†	1/63 (1.59%)	1
Upper Respiratory Infection ^†	1/63 (1.59%)	1
Group A Streptococcus ^†	1/63 (1.59%)	1
Foot Infection ^†	1/63 (1.59%)	1
Kidney Infection ^†	1/63 (1.59%)	1
Injury, poisoning and procedural complications
Femur Fracture ^†	1/63 (1.59%)	1
Investigations
Platelet Count Decreased ^†	2/63 (3.17%)	2
Neutrophil count Decreased ^†	1/63 (1.59%)	1
Metabolism and nutrition disorders
Dehydration ^†	1/63 (1.59%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease Transformation DLBCL ^†	2/63 (3.17%)	2
Myelodysplastic Syndrome ^†	1/63 (1.59%)	1
Adenocarcinoma of the rectum ^†	1/63 (1.59%)	1
Squamous cell carcinoma ^†	2/63 (3.17%)	2
Prostate Cancer ^†	1/63 (1.59%)	1
Nervous system disorders
Syncope ^†	1/63 (1.59%)	1
Psychiatric disorders
Depression and Suicidal Ideation ^†	1/63 (1.59%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion ^†	2/63 (3.17%)	2
Vascular disorders
Hematoma ^†	1/63 (1.59%)	1
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment Arm
	Affected / at Risk (%)	# Events
Total	62/63 (98.41%)
Blood and lymphatic system disorders
Anemia ^†	40/63 (63.49%)	40
Febrile Neutropenia ^†	2/63 (3.17%)	2
Leukocytosis ^†	1/63 (1.59%)	1
Cardiac disorders
Atrial Fibrillation ^†	9/63 (14.29%)	9
Palpiatations ^†	3/63 (4.76%)	3
Sick sinus syndrome ^†	1/63 (1.59%)	1
Sinus bradycardia ^†	2/63 (3.17%)	2
Sinus tachycardia ^†	2/63 (3.17%)	2
Ventricular arrhythmia ^†	1/63 (1.59%)	1
Ear and labyrinth disorders
Hearing impaired ^†	1/63 (1.59%)	1
Tinnitis ^†	2/63 (3.17%)	2
Endocrine disorders
Hypothyroidism ^†	1/63 (1.59%)	1
Eye disorders
Blurred vision ^†	7/63 (11.11%)	7
Cataract ^†	1/63 (1.59%)	1
Conjunctivitis ^†	1/63 (1.59%)	1
Eye pain ^†	2/63 (3.17%)	2
Retinal detachment ^†	2/63 (3.17%)	2
Retinal tear ^†	1/63 (1.59%)	1
Watering eyes ^†	1/63 (1.59%)	1
Gastrointestinal disorders
Abdominal Pain ^†	7/63 (11.11%)	7
Bloating ^†	3/63 (4.76%)	3
Constipation ^†	8/63 (12.70%)	8
Diarrhea ^†	20/63 (31.75%)	20
Duodenal ulcer ^†	1/63 (1.59%)	1
Dyspepsia ^†	1/63 (1.59%)	1
Dysphagia ^†	3/63 (4.76%)	3
Gastric ulcer ^†	1/63 (1.59%)	1
Gastroesophageal reflux disease ^†	12/63 (19.05%)	12
Hemorrhoidal hemmorhage ^†	1/63 (1.59%)	1
Hemorrhoids ^†	1/63 (1.59%)	1
Oral Mucositis ^†	8/63 (12.70%)	8
Nausea ^†	9/63 (14.29%)	9
Oral hemorrhage ^†	4/63 (6.35%)	4
Proctitis ^†	1/63 (1.59%)	1
Rectal perforation ^†	1/63 (1.59%)	1
Small intestinal obstruction ^†	1/63 (1.59%)	1
Toothache ^†	1/63 (1.59%)	1
Vomiting ^†	7/63 (11.11%)	7
General disorders
Chills ^†	3/63 (4.76%)	3
Facial edema ^†	1/63 (1.59%)	1
Edema limbs ^†	9/63 (14.29%)	9
Fatigue ^†	33/63 (52.38%)	33
Fever ^†	13/63 (20.63%)	13
Fly-like symptoms ^†	4/63 (6.35%)	4
Malaise ^†	6/63 (9.52%)	6
Non-cardiac chest pain ^†	2/63 (3.17%)	2
Pain ^†	7/63 (11.11%)	7
Infections and infestations
Bladder Infection ^†	3/63 (4.76%)	3
Bronchial infection ^†	7/63 (11.11%)
Eye infection ^†	1/63 (1.59%)	1
Gum infection ^†	1/63 (1.59%)	1
Lip infection ^†	1/63 (1.59%)	1
Lung infection ^†	14/63 (22.22%)	14
Mucosal infection ^†	3/63 (4.76%)	3
Nail infection ^†	3/63 (4.76%)	3
Otitis media ^†	3/63 (4.76%)	3
Penile Infection ^†	1/63 (1.59%)	1
Pharyngitis ^†	1/63 (1.59%)	1
Sinusitis ^†	21/63 (33.33%)	21
Skin infection ^†	11/63 (17.46%)	11
Soft tissue infection ^†	1/63 (1.59%)	1
Tooth infection ^†	1/63 (1.59%)	1
Upper respiratory infection ^†	19/63 (30.16%)	19
Urinary tract infection ^†	9/63 (14.29%)	9
Vaginal infection ^†	1/63 (1.59%)	1
Wound infection ^†	1/63 (1.59%)	1
Injury, poisoning and procedural complications
Bruising ^†	8/63 (12.70%)	8
Fall ^†	2/63 (3.17%)	2
Fracture ^†	4/63 (6.35%)	4
Wound complication ^†	2/63 (3.17%)	2
Investigations
Alanine aminotransferase increased ^†	2/63 (3.17%)	2
Alkaline phosphatase increased ^†	2/63 (3.17%)	2
Aspartate aminotransferase increased ^†	2/63 (3.17%)	2
Blood bilirubin increased ^†	4/63 (6.35%)	4
Creatinine increased ^†	1/63 (1.59%)	1
Lipase increased ^†	2/63 (3.17%)	2
Neutrophil count decreased ^†	26/63 (41.27%)	26
Platelet count decreased ^†	29/63 (46.03%)	29
Weight gain ^†	2/63 (3.17%)	2
Weight loss ^†	4/63 (6.35%)	4
White blood cell decreased ^†	2/63 (3.17%)	2
Metabolism and nutrition disorders
Anorexia ^†	2/63 (3.17%)	2
Dehydration ^†	4/63 (6.35%)	4
Hypercalcemia ^†	1/63 (1.59%)	1
Hyperglycemia ^†	1/63 (1.59%)	1
Hypoalbuminemia ^†	5/63 (7.94%)	5
Hypoglycemia ^†	1/63 (1.59%)	1
Hypokalemia ^†	4/63 (6.35%)	4
Hypomagnesemia ^†	1/63 (1.59%)	1
Hyponatremia ^†	2/63 (3.17%)	2
Musculoskeletal and connective tissue disorders
Arthralgia ^†	17/63 (26.98%)	17
Back pain ^†	5/63 (7.94%)	5
Bone pain ^†	3/63 (4.76%)	3
Chest wall pain ^†	1/63 (1.59%)	1
Muscle weakness lower limb ^†	1/63 (1.59%)	1
Myalgia ^†	14/63 (22.22%)	14
Neck Pain ^†	1/63 (1.59%)	1
Pain in extremity ^†	2/63 (3.17%)	2
Nervous system disorders
Dizziness ^†	11/63 (17.46%)	11
Dysgeusia ^†	1/63 (1.59%)	1
Headache ^†	11/63 (17.46%)	11
Paresthesia ^†	7/63 (11.11%)	7
Peripheral motor neuropathy ^†	9/63 (14.29%)	9
Peripheral sensory neuropathy ^†	12/63 (19.05%)	12
Stroke ^†	1/63 (1.59%)	1
Syncope ^†	1/63 (1.59%)	1
Psychiatric disorders
Anxiety ^†	6/63 (9.52%)	6
Depression ^†	4/63 (6.35%)	4
Insomnia ^†	5/63 (7.94%)	5
Renal and urinary disorders
Acute kidney injury ^†	1/63 (1.59%)	1
Hematuria ^†	4/63 (6.35%)	4
Renal calculi ^†	2/63 (3.17%)	2
urinary tract obstruction ^†	2/63 (3.17%)	2
Urinary tract pain ^†	1/63 (1.59%)	1
Urinary urgency ^†	2/63 (3.17%)	2
Reproductive system and breast disorders
Irregular menstruation ^†	1/63 (1.59%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^†	1/63 (1.59%)	1
Cough ^†	11/63 (17.46%)	11
Dyspnea ^†	6/63 (9.52%)	6
Epistaxis ^†	8/63 (12.70%)	8
Hypoxia ^†	1/63 (1.59%)	1
Nasal congestion ^†	3/63 (4.76%)	3
Pleural effusion ^†	10/63 (15.87%)	10
Pneumonitis ^†	1/63 (1.59%)	1
Postnasal drip ^†	1/63 (1.59%)	1
Productive cough ^†	1/63 (1.59%)	1
Respiratory failure ^†	1/63 (1.59%)	1
Sore throat ^†	2/63 (3.17%)	2
Wheezing ^†	2/63 (3.17%)	2
Skin and subcutaneous tissue disorders
Alopecia ^†	1/63 (1.59%)	1
Dry eye ^†	1/63 (1.59%)	1
Nail ridging ^†	7/63 (11.11%)	7
Pruritis ^†	5/63 (7.94%)	5
Purpura ^†	1/63 (1.59%)	1
Rash acneiform ^†	3/63 (4.76%)	3
Rash maculo-papular ^†	7/63 (11.11%)	7
scalp pain ^†	1/63 (1.59%)	1
Skin hyperpigmentation ^†	1/63 (1.59%)	1
Urticaria ^†	1/63 (1.59%)	1
Vascular disorders
Hematoma ^†	5/63 (7.94%)	5
Hot flashes ^†	1/63 (1.59%)	1
Hypertension ^†	9/63 (14.29%)	9
Hypotension ^†	2/63 (3.17%)	2
Lymphedema ^†	1/63 (1.59%)	1
† Indicates events were collected by 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

Layout table for Results Point of Contact information

Name/Title:	Dr. Steven Treon
Organization:	Dana-Farber Cancer Institute
Phone:	617-632-2681
EMail:	steven_treon@dfci.harvard.edu

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

Treon SP, Meid K, Gustine J, Yang G, Xu L, Liu X, Patterson CJ, Hunter ZR, Branagan AR, Laubach JP, Ghobrial IM, Palomba ML, Advani R, Castillo JJ. Long-Term Follow-Up of Ibrutinib Monotherapy in Symptomatic, Previously Treated Patients With Waldenström Macroglobulinemia. J Clin Oncol. 2021 Feb 20;39(6):565-575. doi: 10.1200/JCO.20.00555. Epub 2020 Sep 15.

Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, Argyropoulos KV, Yang G, Cao Y, Xu L, Patterson CJ, Rodig S, Zehnder JL, Aster JC, Harris NL, Kanan S, Ghobrial I, Castillo JJ, Laubach JP, Hunter ZR, Salman Z, Li J, Cheng M, Clow F, Graef T, Palomba ML, Advani RH. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med. 2015 Apr 9;372(15):1430-40. doi: 10.1056/NEJMoa1501548.

Layout table for additonal information

Responsible Party:	Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT01614821
Other Study ID Numbers:	12-015
First Submitted:	May 17, 2012
First Posted:	June 8, 2012
Results First Submitted:	November 13, 2019
Results First Posted:	January 21, 2020
Last Update Posted:	January 21, 2020