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
  Purpose

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.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: PCI-32765
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 115
Study Start Date: February 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01236391

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

Additional Information:
No publications provided by Pharmacyclics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01236391     History of Changes
Other Study ID Numbers: PCYC-1104-CA, PCI-32765
Study First Received: October 18, 2010
Results First Received: February 12, 2015
Last Updated: August 24, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Ethics Commission
Germany: Ministry of Health
Poland: Ethics Committee
Poland: Ministry of Health

Keywords provided by Pharmacyclics:
Pharmacyclics
Mantle
Mantle Cell
Lymphoma
Non-Hodgkins
Bortezomib
Velcade
Naive
PCYC

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on September 02, 2015