Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01980628
Recruitment Status : Completed
First Posted : November 11, 2013
Results First Posted : February 10, 2017
Last Update Posted : October 16, 2019
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Tracking Information
First Submitted Date  ICMJE October 29, 2013
First Posted Date  ICMJE November 11, 2013
Results First Submitted Date  ICMJE December 20, 2016
Results First Posted Date  ICMJE February 10, 2017
Last Update Posted Date October 16, 2019
Study Start Date  ICMJE December 2013
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 4, 2013)
To evaluate efficacy using the Overall Response Rate (ORR) in subjects with MZL [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2013)
  • To evaluate efficacy parameter such as duration of response (DOR) to ibrutinib in subjects with MZL [ Time Frame: 3 years ]
  • Frequency, severity, and relatedness of adverse events [ Time Frame: 3 years ]
  • To determine the plasma pharmacokinetics of ibrutinib and the metabolite, PCI-45227 [ Time Frame: 3 years ]
  • To evaluate efficacy parameter such as progression-free survival (PFS) to ibrutinib in subjects with MZL [ Time Frame: 3 years ]
  • To evaluate efficacy parameter such as overall survival (OS) to ibrutinib in subjects with MZL [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: November 4, 2013)
To evaluate prognostic and predictive biomarkers relative to treatment outcomes [ Time Frame: 3 years ]
 
Descriptive Information
Brief Title  ICMJE Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed/Refractory Marginal Zone Lymphoma
Official Title  ICMJE A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Subjects With Relapsed/Refractory Marginal Zone Lymphoma
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Marginal Zone Lymphoma
  • B-cell Lymphoma
Intervention  ICMJE Drug: ibrutinib
Other Name: PCI-32765
Study Arms  ICMJE Experimental: ibrutinib
ibrutinib capsules: 560 mg once daily
Intervention: Drug: ibrutinib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 16, 2016)
63
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2013)
60
Actual Study Completion Date  ICMJE October 2, 2017
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01980628
Other Study ID Numbers  ICMJE PCYC-1121-CA
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmacyclics LLC.
Study Sponsor  ICMJE Pharmacyclics LLC.
Collaborators  ICMJE Janssen Research & Development, LLC
Investigators  ICMJE
Study Director: Isaiah Dimery, MD Pharmacyclics LLC.
PRS Account Pharmacyclics LLC.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP