Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL) (PCYC-1104-CA)

Tracking Information
First Submitted Date ICMJE	October 18, 2010
First Posted Date ICMJE	November 8, 2010
Results First Submitted Date	February 12, 2015
Results First Posted Date	March 13, 2015
Last Update Posted Date	August 28, 2015
Study Start Date ICMJE	February 2011
Actual Primary Completion Date	January 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 4, 2015)	Percentage of Participants Achieving Response [ Time Frame: The median follow-up time on study for all treated participants is 15.3 (range 1.9 - 22.3) months ]; 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. CR is a complete disappearance of all disease, no new lesions, lymph nodes must have regressed and be PET negative, spleen and liver should not be palpable and without nodules, and bone marrow must be negative. PR is a >/= 50% decrease in the sum of the product of diameters of the target lesions, and >/= 50% decrease of splenic and hepatic nodules from baseline, no new lesions and no increase in the size of liver, spleen or non-target lesions.
Original Primary Outcome Measures ICMJE; (submitted: November 5, 2010)	To Measure the Number of Participants with a Response to Study Drug [ Time Frame: Participants will be followed until progression of disease or start of another anti-cancer treatment. ]
Change History	Complete list of historical versions of study NCT01236391 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 4, 2015)	Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure ]Number of participants who had experienced at least one treatment emergent AE; PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765 [ Time Frame: Performed During the First Month of Receiving PCI-32765 ]Area under the plasma concentration-time curve using data collected at 0, 1, 2, 4, 6-8, and 24 hours post dose (AUC0-24h); Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score [ Time Frame: From Baseline to Cycle 5 (Week 20) ]Mean change from baseline to Cycle 5 in the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) Global Health Status Score according to EORTC QLQ-C30 Scoring Manual (3rd Edition, 2001). For global health status, positive changes indicated better health status or functioning, and negative changes indicated worsening of health status or functioning. Scale scores range from 0 to 100. A change in 5 to 10 points in either direction represents a small change; 10 to 20 points represents a moderate change and greater than 20 points represents a large change.
Original Secondary Outcome Measures ICMJE; (submitted: November 5, 2010)	To Measure the Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Participants will be followed until progression of disease or start of another anti-cancer treatment. ]; To Measure the Number of Participants Pharmacokinetics to Assist in Determining How the Body Responds to the Study Drug [ Time Frame: Procedure to be Performed During the First Month of Receiving Study Drug. ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)
Official Title ICMJE	Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma
Brief Summary	The primary objective of this study was to evaluate the efficacy of ibrutinib in participants with relapsed or refractory MCL. The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg daily) of PCI-32765 in this population.
Detailed Description	This is a Phase 2, open-label, nonrandomized, multicenter, monotherapy study in subjects with histologically documented MCL who have relapsed after ≥ 1 (but not > 5) prior treatment regimens. All subjects meeting eligibility criteria will receive PCI-32765 capsules at a dosage of 560 mg/day once daily for a 28-day cycle until disease progression, unacceptable toxicity, or enrollment in a long-term extension study, whichever occurs earlier.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Mantle Cell Lymphoma
Intervention ICMJE	Drug: PCI-32765; 560 mg daily
Study Arms	Experimental: Participants received PCI-32765 560 mg daily; Participants were enrolled and received 560 mg/day dose, stratified into 2 groups based on prior bortezomib exposure.; Intervention: Drug: PCI-32765
Publications *	Wang ML, Blum KA, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Zhang L, Baher L, Cheng M, Lee D, Beaupre DM, Rule S. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015 Aug 6;126(6):739-45. doi: 10.1182/blood-2015-03-635326. Epub 2015 Jun 9.; Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, De Nicolao G, O'Brien S, Byrd JC, Advani R, McGreivy J, Poggesi I. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015 Jan;75(1):111-21. doi: 10.1007/s00280-014-2617-3. Epub 2014 Nov 8.; Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 30, 2011)	115
Original Estimated Enrollment ICMJE; (submitted: November 5, 2010)	50
Actual Study Completion Date	January 2014
Actual Primary Completion Date	January 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Men and women ≥ 18 years of age; ECOG performance status of ≤ 2; Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or t(11;14), and measurable disease on cross sectional imaging that is ≥ 2 cm in the longest diameter and measurable in 2 perpendicular dimensions; Documented failure to achieve at least partial response (PR) with, or documented disease progression disease after, the most recent treatment regimen; At least 1, but no more than 5, prior treatment regimens for MCL (Note: Subjects having received ≥2 cycles of prior treatment with bortezomib, either as a single agent or as part of a combination therapy regimen, will be considered to be bortezomib-exposed.); Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty; Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations) Major exclusion criteria: Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy within 3 weeks, or major surgery within 2 weeks of first dose of study drug; Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk; Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification; Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction; Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is documented bone marrow involvement Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion support unless there is documented bone marrow involvement Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) Creatinine > 2.0 x ULN
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Germany, Poland, United Kingdom, United States
Removed Location Countries	Austria
Administrative Information
NCT Number ICMJE	NCT01236391
Other Study ID Numbers ICMJE	PCYC-1104-CA; PCI-32765 ( Other Identifier: Pharmacyclics )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Pharmacyclics LLC.
Study Sponsor ICMJE	Pharmacyclics LLC.
Collaborators ICMJE	Janssen Pharmaceuticals
Investigators ICMJE	Study Director: Darrin Beaupre, MD, PhD Pharmacyclics LLC.
PRS Account	Pharmacyclics LLC.
Verification Date	August 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP