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

Marginal Zone Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01980628
• Other study ID #: PCYC-1121-CA
• Status: Completed
• Phase: Phase 2
• Start date: December 2013
• Est. completion date: October 2, 2017

Study information

• Verified date: October 2019
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: October 2, 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Marginal Zone Lymphoma

Intervention

Drug:
• ibrutinib

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Pharmacyclics LLC.	Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
Secondary	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.	Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.