Clinical trial NCT01980628: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Marginal Zone Lymphoma
B-cell Lymphoma
Keywords: MZL
NHL
SMZL
NMZL
MALT
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2013-11-11
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: ORR (Overall Response Rate)
timeFrame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
Secondary outcomes:
measure: DOR (Duration of Response)
timeFrame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Site Reference ID/Investigator# 837
state: Arizona
city: Duarte
country: United States
facility: Site Reference ID/Investigator# 047
state: California
city: Santa Monica
country: United States
facility: Site Reference ID/Investigator# 377
state: California
city: West Palm Beach
country: United States
facility: Site Reference ID/Investigator# 763
state: Florida
city: Atlanta
country: United States
facility: Site Reference ID/Investigator# 033
state: Georgia
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 370
state: Illinois
city: Detroit
country: United States
facility: Site Reference ID/Investigator# 195
state: Michigan
city: New Hyde Park
country: United States
facility: Site Reference ID/Investigator# 350
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator# 745
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator # 200
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator # 407
state: New York
city: Hershey
country: United States
facility: Site Reference ID/Investigator# 220
state: Pennsylvania
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 348
state: Washington
city: Ghent
country: Belgium
facility: Site Reference ID/Investigator# 560
state: Oost-vlaanderen
city: Rouen Cedex 1
country: France
facility: Site Reference ID/Investigator# 737
state: Haute-normandie
city: Paris Cedex 10
country: France
facility: Site Reference ID/Investigator# 735
state: Ile-de-france
city: Lille Cedex
country: France
facility: Site Reference ID/Investigator# 750
state: NORD Pas-de-calais
city: La Roche-sur-Yon Cedex 9
country: France
facility: Site Reference ID/Investigator# 749
state: PAYS DE LA Loire
city: Nantes cedex 1
country: France
facility: Site Reference ID/Investigator# 736
state: PAYS DE LA Loire
city: Pierre Bénite Cedex
country: France
facility: Site Reference ID/Investigator# 142
state: Rhone-alpes
city: Rennes cedex 9
country: France
facility: Site Reference ID/Investigator# 742
city: Mainz
country: Germany
facility: Site Reference ID/Investigator# 669
state: Rheinland-Pfalz
city: Manchester
country: United Kingdom
facility: Site Reference ID/Investigator# 030
state: England
city: Oxford
country: United Kingdom
facility: Site Reference ID/Investigator# 814
state: England
city: Plymouth
country: United Kingdom
facility: Site Reference ID/Investigator# 368
state: England
Study officials:
affiliation: Pharmacyclics LLC.
name: Isaiah Dimery, MD
role: STUDY_DIRECTOR
References:
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.
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.