Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed/Refractory Marginal Zone Lymphoma

October 8, 2019 updated by: Pharmacyclics LLC.

A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Subjects With Relapsed/Refractory Marginal Zone Lymphoma

Phase 2, open-label, non-randomized, monotherapy study to evaluate the safety and efficacy of ibrutinib in subject with relapsed/refractory Marginal Zone Lymphoma (MZL).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Ibrutinib is a first-in-class, potent, orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK). Inhibition of BTK blocks downstream B-cell receptor (BCR) signaling pathways and thus prevents B-cell proliferation. In vitro, ibrutinib inhibits purified BTK and selected members of the kinase family with 10-fold specificity compared with non-BTK kinases. Phase 1 and 2 studies of ibrutinib in B-cell malignancies demonstrate modest toxicity and significant single agent activity in a variety of B-cell malignancies, including NHL.

Study Type

Interventional

Enrollment (Actual)

63

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

  • Belgium
    • Oost-vlaanderen
      • Ghent, Oost-vlaanderen, Belgium
        • Site Reference ID/Investigator# 560
  • France
      • Rennes cedex 9, France
        • Site Reference ID/Investigator# 742
    • Haute-normandie
      • Rouen Cedex 1, Haute-normandie, France
        • Site Reference ID/Investigator# 737
    • Ile-de-france
      • Paris Cedex 10, Ile-de-france, France
        • Site Reference ID/Investigator# 735
    • NORD Pas-de-calais
      • Lille Cedex, NORD Pas-de-calais, France
        • Site Reference ID/Investigator# 750
    • PAYS DE LA Loire
      • La Roche-sur-Yon Cedex 9, PAYS DE LA Loire, France
        • Site Reference ID/Investigator# 749
      • Nantes cedex 1, PAYS DE LA Loire, France
        • Site Reference ID/Investigator# 736
    • Rhone-alpes
      • Pierre Bénite Cedex, Rhone-alpes, France
        • Site Reference ID/Investigator# 142
  • Germany
    • Rheinland-Pfalz
      • Mainz, Rheinland-Pfalz, Germany
        • Site Reference ID/Investigator# 669
  • United Kingdom
    • England
      • Manchester, England, United Kingdom
        • Site Reference ID/Investigator# 030
      • Oxford, England, United Kingdom
        • Site Reference ID/Investigator# 814
      • Plymouth, England, United Kingdom
        • Site Reference ID/Investigator# 368
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Site Reference ID/Investigator# 837
    • California
      • Duarte, California, United States, 91010
        • Site Reference ID/Investigator# 047
      • Santa Monica, California, United States, 90095
        • Site Reference ID/Investigator# 377
    • Florida
      • West Palm Beach, Florida, United States, 33401
        • Site Reference ID/Investigator# 763
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Site Reference ID/Investigator# 033
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Site Reference ID/Investigator# 370
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Site Reference ID/Investigator# 195
    • New York
      • New Hyde Park, New York, United States, 11042
        • Site Reference ID/Investigator# 350
      • New York, New York, United States, 08724
        • Site Reference ID/Investigator# 745
      • New York, New York, United States, 10065
        • Site Reference ID/Investigator # 200
      • New York, New York, United States, 10065
        • Site Reference ID/Investigator # 407
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Site Reference ID/Investigator# 220
    • Washington
      • Seattle, Washington, United States, 98109
        • Site Reference ID/Investigator# 348

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

Key Inclusion criteria:

  • Histologically documented marginal zone lymphoma including splenic, nodal, and extranodal sub-types; subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criteria 5
  • Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least PR or documented PD after, the most recent systemic treatment regimen
  • Men and women ≥18 years of age
  • ECOG performance status of ≤2
  • ≥1 measurable lesion site on CT scan (>1.5 cm in longest dimension). Lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by MRI instead. (Subjects with spleen-only disease are considered as not having measurable disease.)
  • Life expectancy of >3 months, in the opinion of the investigator

Key Exclusion criteria:

  • Medically apparent CNS lymphoma or leptomeningeal disease
  • History of other malignancies except adequately treated non melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥2 years
  • History of allogeneic stem-cell (or other organ) transplantation
  • Any chemotherapy, anticancer antibodies, or other systemic anticancer therapy within 21 days of the first dose of study drug
  • Any external beam radiation therapy within 6 weeks prior to the first dose of the study drug
  • Concurrent use of warfarin or other vitamin K antagonists
  • Concurrent use of a strong CYP3A inhibitor. Subjects who have received a strong CYP3A inhibitor prior to entering the study must have discontinued therapy for at least 5 half lives of the prohibited medication.
  • Recent infection requiring IV anti-infective treatment that was completed ≤14 days before the first dose of study drug
  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to CTCAE Grade 0 or 1, or to the levels dictated in the eligibility criteria with the exception of alopecia
  • Inadequate organ function as defined on laboratory tests

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ibrutinib
ibrutinib capsules: 560 mg once daily
Drug: ibrutinib
Other Names:
  • PCI-32765

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR (Overall Response Rate)
Time Frame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.

ORR is defined as the proportion of subjects who achieved complete response (CR), partial response (PR). Response criteria are as outlined in the International Working Group Criteria for NHL, Cheson (2007), with disease assessments performed by an independent review committee (IRC).

Per Cheson:

CR is defined as disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites.
Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DOR (Duration of Response)
Time Frame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
The DOR analyses is performed on the subset of subjects that achieve CR or PR as determined by IRC. DOR is calculated as the duration of time from the date of first response to the date of progression or death due to any cause.
Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.

Collaborators and Investigators

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

Sponsor

Pharmacyclics LLC.

Collaborators

Janssen Research & Development, LLC

Investigators

  • Study Director: Isaiah Dimery, 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

December 1, 2013

Primary Completion (ACTUAL)

July 1, 2016

Study Completion (ACTUAL)

October 2, 2017

Study Registration Dates

First Submitted

October 29, 2013

First Submitted That Met QC Criteria

November 4, 2013

First Posted (ESTIMATE)

November 11, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 16, 2019

Last Update Submitted That Met QC Criteria

October 8, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-1121-CA

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.

Clinical Trials on B-cell Lymphoma

Clinical Trials on ibrutinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Iran

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe