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

This study is ongoing, but not recruiting participants.
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics Identifier:
First received: October 29, 2013
Last updated: April 8, 2016
Last verified: April 2016
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).

Condition Intervention Phase
Marginal Zone Lymphoma
B-cell Lymphoma
Drug: ibrutinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • To evaluate efficacy using the Overall Response Rate (ORR) as assessed by an Independent Review Committee (IRC) in subjects with MZL [ Time Frame: At the earliest, 52 weeks after last patient enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate efficacy parameter such as duration of response (DOR) to ibrutinib in subjects with MZL [ Time Frame: At the earliest, 52 weeks after last patient enrolled ] [ Designated as safety issue: No ]
  • Frequency, severity, and relatedness of adverse events [ Time Frame: At the earliest, 52 weeks after last patient enrolled ] [ Designated as safety issue: Yes ]
  • To determine the plasma pharmacokinetics of ibrutinib and the metabolite, PCI-45227 [ Time Frame: At the earliest, 52 weeks after last patient enrolled ] [ Designated as safety issue: No ]
  • To evaluate efficacy parameter such as progression-free survival (PFS) to ibrutinib in subjects with MZL [ Time Frame: At the earliest, 52 weeks after last patient enrolled ] [ Designated as safety issue: No ]
  • To evaluate efficacy parameter such as overall survival (OS) to ibrutinib in subjects with MZL [ Time Frame: At the earliest, 52 weeks after last patient enrolled ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • To evaluate prognostic and predictive biomarkers relative to treatment outcomes [ Time Frame: At the earliest, 52 weeks after last patient enrolled ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: December 2013
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ibrutinib
ibrutinib capsules: 560 mg once daily
Drug: ibrutinib

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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01980628

  Show 26 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Study Director: Isaiah Dimery, MD Pharmacyclics
  More Information

Responsible Party: Pharmacyclics Identifier: NCT01980628     History of Changes
Other Study ID Numbers: PCYC-1121-CA 
Study First Received: October 29, 2013
Last Updated: April 8, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Germany: Federal Institute for Drugs and Medical Devices
France: Agence Nationale de Sécurité du Médicament et des produits de santé
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service

Keywords provided by Pharmacyclics:

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms by Histologic Type processed this record on May 25, 2016