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

This study has been completed.

Sponsor:

Collaborator:

Janssen Pharmaceuticals

Information provided by (Responsible Party):

Pharmacyclics

ClinicalTrials.gov Identifier:

NCT01236391

First received: October 18, 2010

Last updated: August 24, 2015

Last verified: August 2015

History of Changes

Tracking Information

First Received Date ^ICMJE

October 18, 2010

Last Updated Date

August 24, 2015

Start Date ^ICMJE

February 2011

Primary Completion Date

January 2014 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ] [ Designated as safety issue: No ]

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

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. ] [ Designated as safety issue: No ]

Change History

Complete list of historical versions of study NCT01236391 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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

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. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: Yes ]

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

Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Mantle Cell Lymphoma

Intervention ^ICMJE

Drug: PCI-32765

560 mg daily

Study Arm (s)

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 *

* 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

Enrollment ^ICMJE

115

Completion Date

January 2014

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:
1. Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is documented bone marrow involvement
2. Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion support unless there is documented bone marrow involvement
3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)
4. Creatinine > 2.0 x ULN

Gender

Both

Ages

18 Years and older (Adult, Senior)

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States, Germany, Poland, United Kingdom

Removed Location Countries

Austria

Administrative Information

NCT Number ^ICMJE

NCT01236391

Other Study ID Numbers ^ICMJE

PCYC-1104-CA, PCI-32765

Has Data Monitoring Committee

Plan to Share Data

Not Provided

IPD Description

Not Provided

Responsible Party

Pharmacyclics

Study Sponsor ^ICMJE

Pharmacyclics

Collaborators ^ICMJE

Janssen Pharmaceuticals

Investigators ^ICMJE

Study Director:

Darrin Beaupre, MD, PhD

Pharmacyclics

Information Provided By

Pharmacyclics

Verification Date

August 2015

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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