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Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

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: NCT01325701
Recruitment Status : Completed
First Posted : March 30, 2011
Results First Posted : February 16, 2017
Last Update Posted : March 31, 2017
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.

Study Description
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Brief Summary:
The purpose of this study is to evaluate the efficacy of ibrutinib (PCI-32765) in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).

Condition or disease Intervention/treatment Phase
Diffuse Large Cell B-lymphoma Drug: ibrutinib Phase 2

Detailed Description:

The primary objectives of this study were to evaluate the efficacy of ibrutinib administered at 560 mg once per day in relapsed or refractory de novo ABC and GCB DLBCL, and to evaluate the efficacy of ibrutinib administered at 840 mg once per day in relapsed or refractory de novo ABC DLBCL.

The secondary objective was to evaluate the safety and tolerability of a fixed daily oral dosing regimen of ibrutinib in relapsed/refractory de novo DLBCL.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Phase 2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Refractory or de Novo Diffuse Large B-cell Lymphoma (DLBCL)
Study Start Date : May 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Ibrutinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: PCI-32765: 560 mg
Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.
 Drug: ibrutinib
ibrutinib is an inhibitor of BTK
Other Name: PCI-32765, Imbruvica
Experimental: PCI-32765: 840 mg
Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
 Drug: ibrutinib
ibrutinib is an inhibitor of BTK
Other Name: PCI-32765, Imbruvica


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Patients With an Overall Response to Study Drug [ Time Frame: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 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.


Secondary Outcome Measures :
  1. Number of Patients With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years). ]
    Participants will be followed until progression of the disease or start of another anticancer treatment. The clinical database captured all AEs from baseline through end of treatment. Treatment Emergent AEs were collected pre-dose, at the beginning of each cycle and 30 days post last dose of study drug, unless related to study drug.

  2. Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765 [ Time Frame: Performed during the first month of receiving study drug. ]

    Treatment Group 1 PK collection schedule:

    Cycle 1 Day 1: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 8: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose

    Treatment Group 2 PK collection schedule:

    Cycle 1 Day 8: Pre-dose, 1, 2, 4 and 7 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Cycle 3 Day 1: Pre-dose, 1, 2, and 4 hours post-dose



Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women ≥ 18 years of age.
  2. ECOG performance status ≤ 2.
  3. Pathologically confirmed de novo DLBCL
  4. Subjects must have available tissue for central pathology review to be eligible. Treatment Group 2: Subjects will be eligible if they have the non-GCB phenotype, as confirmed by Central IHC testing by the Hans method.
  5. Relapsed or refractory disease, defined as either: 1) recurrence of disease after a CR, or 2) PR, SD, or progressive disease (PD) at completion of the treatment regimen preceding entry to the study (residual disease): Subjects must have previously received an appropriate first-line treatment regimen. Subjects who have not received HDT/ASCT must be ineligible for HDT/ASCT
  6. Treatment Group 1: Subjects must have ≥ 1 measurable (> 2 cm in longest dimension) disease sites on CT scan. Treatment Group 2: Subjects must have ≥ 1 measurable (> 1.5 cm in longest dimension) disease sites on CT scan.

Exclusion Criteria:

  1. Transformed DLBCL or DLBCL with coexistent histologies (eg, FL or MALT).
  2. Primary mediastinal (thymic) large B-cell lymphoma.
  3. Known central nervous system lymphoma. In addition, for subjects in Treatment Group 2, known leptomeningeal involvement is exclusionary.
  4. Certain exclusions on prior therapy
  5. Major surgery within 2 weeks of first dose of study drug.

  6. Any of the following laboratory abnormalities:

    1. ANC < 0.75 x 10^9/L. Treatment Group 2: Eligible subjects must be independent of growth factor support for 7 days prior to the screening lab tests.
    2. Platelet count < 50 x 10^9/L independent of transfusion support. Treatment Group 2 only: Eligible subjects must be independent of transfusion support for 7 days prior to the screening lab tests.
    3. AST or ALT ≥ 3.0 x upper limit of normal (ULN)
    4. Creatinine > 2.0 x ULN
    5. Treatment Group 2 only: Hemoglobin < 8.0 g/dL
    6. Treatment Group 2 only: Total Bilirubin > 1.5 x ULN
  7. Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon)
  8. Treatment Group 2: Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
  9. Treatment Group 2: Known bleeding diathesis, eg, von Willebrand's disease, hemophilia.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01325701


Locations
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United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Maryland
National Cancer Institute
Bethesda, Maryland, United States, 20892-1203
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11042
New York University
New York, New York, United States, 10016
Weill Medical College of Cornell University
New York, New York, United States, 10021
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
University of Rochester School of Medicine and Dentistry
Rochester, New York, United States, 14642
United States, Ohio
The Ohio Sate university
Columbus, Ohio, United States, 43210
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Univerity of Washington
Seattle, Washington, United States, 98109
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
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Study Director: Darrin Beaupre, MD Pharmacyclics LLC.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT01325701    
Other Study ID Numbers: PCYC-1106-CA
PCI-32765 ( Other Identifier: Pharmacyclics )
First Posted: March 30, 2011    Key Record Dates
Results First Posted: February 16, 2017
Last Update Posted: March 31, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Pharmacyclics LLC.:
PCI-32765
Lymphoma, B-Cell
Bruton's Tyrosine Kinase
 Non Hodgkin's Lymphoma
Germinal Center B-Cell
Activated B-Cell
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin