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

Primary Purpose

Marginal Zone Lymphoma, B-cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ibrutinib
Sponsored by
Pharmacyclics LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Marginal Zone Lymphoma focused on measuring MZL, NHL, SMZL, NMZL, MALT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Site Reference ID/Investigator# 837
  • Site Reference ID/Investigator# 047
  • Site Reference ID/Investigator# 377
  • Site Reference ID/Investigator# 763
  • Site Reference ID/Investigator# 033
  • Site Reference ID/Investigator# 370
  • Site Reference ID/Investigator# 195
  • Site Reference ID/Investigator# 350
  • Site Reference ID/Investigator# 745
  • Site Reference ID/Investigator # 200
  • Site Reference ID/Investigator # 407
  • Site Reference ID/Investigator# 220
  • Site Reference ID/Investigator# 348
  • Site Reference ID/Investigator# 560
  • Site Reference ID/Investigator# 737
  • Site Reference ID/Investigator# 735
  • Site Reference ID/Investigator# 750
  • Site Reference ID/Investigator# 749
  • Site Reference ID/Investigator# 736
  • Site Reference ID/Investigator# 142
  • Site Reference ID/Investigator# 742
  • Site Reference ID/Investigator# 669
  • Site Reference ID/Investigator# 030
  • Site Reference ID/Investigator# 814
  • Site Reference ID/Investigator# 368

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ibrutinib

Arm Description

ibrutinib capsules: 560 mg once daily

Outcomes

Primary Outcome Measures

ORR (Overall Response Rate)
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.

Secondary Outcome Measures

DOR (Duration of Response)
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.

Full Information

First Posted
October 29, 2013
Last Updated
October 8, 2019
Sponsor
Pharmacyclics LLC.
Collaborators
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01980628
Brief Title
Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed/Refractory Marginal Zone Lymphoma
Official Title
A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Subjects With Relapsed/Refractory Marginal Zone Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
October 2, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
Collaborators
Janssen Research & Development, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Marginal Zone Lymphoma, B-cell Lymphoma
Keywords
MZL, NHL, SMZL, NMZL, MALT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ibrutinib
Arm Type
Experimental
Arm Description
ibrutinib capsules: 560 mg once daily
Intervention Type
Drug
Intervention Name(s)
ibrutinib
Other Intervention Name(s)
PCI-32765
Primary Outcome Measure Information:
Title
ORR (Overall Response Rate)
Description
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.
Time Frame
Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
Secondary Outcome Measure Information:
Title
DOR (Duration of Response)
Description
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.
Time Frame
Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Isaiah Dimery, MD
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 837
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Site Reference ID/Investigator# 047
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Site Reference ID/Investigator# 377
City
Santa Monica
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Site Reference ID/Investigator# 763
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
Site Reference ID/Investigator# 033
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Site Reference ID/Investigator# 370
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Site Reference ID/Investigator# 195
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Site Reference ID/Investigator# 350
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Site Reference ID/Investigator# 745
City
New York
State/Province
New York
ZIP/Postal Code
08724
Country
United States
Facility Name
Site Reference ID/Investigator # 200
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Site Reference ID/Investigator # 407
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Site Reference ID/Investigator# 220
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Site Reference ID/Investigator# 348
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Site Reference ID/Investigator# 560
City
Ghent
State/Province
Oost-vlaanderen
Country
Belgium
Facility Name
Site Reference ID/Investigator# 737
City
Rouen Cedex 1
State/Province
Haute-normandie
Country
France
Facility Name
Site Reference ID/Investigator# 735
City
Paris Cedex 10
State/Province
Ile-de-france
Country
France
Facility Name
Site Reference ID/Investigator# 750
City
Lille Cedex
State/Province
NORD Pas-de-calais
Country
France
Facility Name
Site Reference ID/Investigator# 749
City
La Roche-sur-Yon Cedex 9
State/Province
PAYS DE LA Loire
Country
France
Facility Name
Site Reference ID/Investigator# 736
City
Nantes cedex 1
State/Province
PAYS DE LA Loire
Country
France
Facility Name
Site Reference ID/Investigator# 142
City
Pierre Bénite Cedex
State/Province
Rhone-alpes
Country
France
Facility Name
Site Reference ID/Investigator# 742
City
Rennes cedex 9
Country
France
Facility Name
Site Reference ID/Investigator# 669
City
Mainz
State/Province
Rheinland-Pfalz
Country
Germany
Facility Name
Site Reference ID/Investigator# 030
City
Manchester
State/Province
England
Country
United Kingdom
Facility Name
Site Reference ID/Investigator# 814
City
Oxford
State/Province
England
Country
United Kingdom
Facility Name
Site Reference ID/Investigator# 368
City
Plymouth
State/Province
England
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33227125
Citation
Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. doi: 10.1182/bloodadvances.2020003121.
Results Reference
derived
PubMed Identifier
28167659
Citation
Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. doi: 10.1182/blood-2016-10-747345. Epub 2017 Feb 6.
Results Reference
derived

Learn more about this trial

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

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