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

March 2, 2017 updated by: Pharmacyclics LLC.

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)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

78

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

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine
    • Maryland
      • Bethesda, Maryland, United States, 20892-1203
        • National Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New Hyde Park, New York, United States, 11042
        • Long Island Jewish Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • New York University
      • New York, New York, United States, 10021
        • Weill Medical College of Cornell University
      • Rochester, New York, United States, 14642
        • University of Rochester School of Medicine and Dentistry
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio Sate University
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Univerity of Washington
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • 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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • PCI-32765, Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).
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
Performed during the first month of receiving study drug.

Collaborators and Investigators

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

Sponsor

Pharmacyclics LLC.

Investigators

  • Study Director: Darrin Beaupre, MD, 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

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

May 1, 2011

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

February 2, 2011

First Submitted That Met QC Criteria

March 29, 2011

First Posted (Estimate)

March 30, 2011

Study Record Updates

Last Update Posted (Actual)

March 31, 2017

Last Update Submitted That Met QC Criteria

March 2, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-1106-CA
  • PCI-32765 (Other Identifier: Pharmacyclics)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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