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

August 24, 2015 updated by: Pharmacyclics LLC.

Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

115

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munchen, Germany, D - 81377
        • Klinikum der Universität München - Campus Grosshadern
      • ULM, Germany, 89081
        • Universitätsklinikum Ulm, Klinik für Innere Medizin II
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Oddzail Kliniczny Onkologil
      • Krakow, Poland, 30-510
        • Malopolskie Centrum Medyczne
      • Warsaw, Poland, 02-106
        • MTZ Clinical Research Sp. z o.o.
  • United Kingdom
      • London, United Kingdom, EC1M6BQ
        • Centre for Experimental Cancer Medicine
      • Manchester, United Kingdom, M20 4BX
        • Christie Hospital
      • Plymouth, United Kingdom, PL6 8DH
        • Derriford Hospital
      • Southampton, United Kingdom, SO16 6YD
        • Southampton General Hospital
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New Hyde Park, New York, United States, 11042
        • CLL Research and Treatment Program
      • New York, New York, United States, 94305
        • New York Presbyterian Hospital/Cornell Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio Sate University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia School of Medicine Hospital
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: PCI-32765
560 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
The median follow-up time on study for all treated participants is 15.3 (range 1.9 - 22.3) months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure
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)
Performed During the First Month of Receiving PCI-32765
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.
From Baseline to Cycle 5 (Week 20)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharmacyclics LLC.

Collaborators

Janssen Pharmaceuticals

Investigators

  • Study Director: Darrin Beaupre, MD, PhD, Pharmacyclics LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

October 18, 2010

First Submitted That Met QC Criteria

November 5, 2010

First Posted (Estimate)

November 8, 2010

Study Record Updates

Last Update Posted (Estimate)

August 28, 2015

Last Update Submitted That Met QC Criteria

August 24, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-1104-CA
  • PCI-32765 (Other Identifier: Pharmacyclics)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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