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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Pharmacyclics
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01980628
First received: October 29, 2013
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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: 36 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: 36 weeks after last patient enrolled ] [ Designated as safety issue: No ]
  • Frequency, severity, and relatedness of adverse events [ Time Frame: 36 weeks after last patient enrolled ] [ Designated as safety issue: Yes ]
  • To determine the plasma pharmacokinetics of ibrutinib and the metabolite, PCI-45227 [ Time Frame: 36 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: 36 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: 36 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: 36 weeks after last patient enrolled ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: December 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2015 (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.

  Eligibility

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

Key Inclusion criteria:

  • Histologically documented marginal zone lymphoma (including splenic, nodal, and extranodal sub-types)
  • 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 disease 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.
  • 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 ClinicalTrials.gov identifier: NCT01980628

Contacts
Contact: Susie Tanamly 855-427-8846 medinfo@pcyc.com
Contact: Deepali Suri 855-427-8846 medinfo@pcyc.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Cheryl Corpus    626-256-4673 ext 31311    ccorpus@coh.org   
Principal Investigator: Robert Chen, MD         
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Baudelio Gutierrez    310-582-4046    bgutierrez@mednet.ucla.edu   
Principal Investigator: Sven deVos, MD         
University of California San Diego Moores Cancer Center Recruiting
San Diego, California, United States, 92093
Contact: Jenny Perales    858-822-6937    j7perez@ucsd.edu   
Principal Investigator: Januario Castro, MD         
United States, Florida
Florida Cancer Specialists Recruiting
West Palm Beach, Florida, United States, 33401
Contact: Jennifer Bar-Nur    561-472-1696    jbar-nur@flcancer.com   
Principal Investigator: Robert Jacobson, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Jose Zavala       jose.zavala@northwestern.edu   
Principal Investigator: Shuo Ma, MD, PhD         
United States, Massachusetts
Lahey Clinic Medical Center Recruiting
Burlington, Massachusetts, United States, 01805
Contact: Deborah Gannon, MS    781-744-2734    Deborah.J.Gannon@lahey.org   
Principal Investigator: Hande Tuncer, MD         
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Kathern Thomason    313-916-7827    kthomas9@hfhs.org   
Principal Investigator: Nalini Janakiraman, MD         
United States, New York
Long Island Jewish Medical Center Recruiting
New Hyde Park, New York, United States, 11042
Contact: Alexis Mark    718-470-4743    amark1@nshs.edu   
Principal Investigator: Jacqueline Barrientos, MD         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Lymphoma Service    646-497-9137      
Principal Investigator: Ariela Noy, MD         
Clinical Research Alliance Recruiting
New York, New York, United States, 10021
Contact: Colleen Kats    855-737-2873 ext 121    ckats@researchcra.com   
Principal Investigator: Morton Coleman, MD, FACP         
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: Peter Martin, MD    646-962-2068    pem9019@med.cornell.edu   
Principal Investigator: Peter Martin, MD         
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Christine Capper    717-531-0003 ext 285453    ccapper@hmc.psu.edu   
Principal Investigator: Christopher Ehmann, MD         
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Lacey Hedin    206-667-2731    lhedin@fhcrc.org   
Principal Investigator: Stephen Smith, MD         
Belgium
Universitair Ziekenhuis Gent Recruiting
Ghent, Oost-Vlaanderen, Belgium, 9000
Contact: Sofie Lust    +32 9 332 08 70    sofie.lust@uzgent.be   
Principal Investigator: Fritz Offner         
France
Centre Henri-Becquerel Recruiting
Rouen Cedex 1, Haute-Normandie, France, 76038
Contact: Laure Gaillon    +33232082220    laure.ditullio-gaillon@chb.unicancer.fr   
Principal Investigator: Herve Tilly         
Centre Hospitalier Universitaire Henri Mondor Recruiting
Créteil, Ile de France, France, 94010
Contact: Feriel Bouabbas    +33149814182    feriel.bouabbas@hmn.aphp.fr   
Principal Investigator: Corinne Haioun         
Hôpital Saint Louis Recruiting
Paris Cedex 10, Ile de France, France, 75475
Contact: Patricia D'Agostino    +33142385100    patricia.dagostino@sls.aphp.fr   
Contact: Laurence Culine    +0142385110    laurence.culine@sls.aphp.fr   
Principal Investigator: Catherine Thieblemont         
CHRU de Limoges - Hôpital Dupuytren Recruiting
Limoges Cedex, Limousin, Lorraine, France, 87042
Principal Investigator: Dominique Bordessoule         
Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez Recruiting
Lille Cedex, Nord pas de Calais, France, 59037
Contact: Carole Delecroix    +33320444284    carole.delecroix@chru-lille.fr   
Principal Investigator: Franck Morschhauser         
CHD Vendée, Site de La Roche-sur-Yon, Les Oudairies Recruiting
La Roche-sur-Yon Cedex 9, Pays de la Loire, France
Contact: Hélène Renoul    +33251446467    helene.renoul@chd-vendee.fr   
Principal Investigator: Hervé Maisonneuve         
Centre Hospitalier Universitaire Nantes, Hotel Dieu Recruiting
Nantes cedex 1, Pays de la Loire, France, 44093
Contact: Alexis Morice    +33240084030    alexis.morice@chu-nantes.fr   
Principal Investigator: Steven LeGouill         
Centre Hospitalier Lyon Sud Recruiting
Pierre Bénite Cedex, Rhone- Alpes, France, 69495
Contact: Severine Seemann    +33478864337    severine.seemann@chu-lyon.fr   
Principal Investigator: Gilles Salles         
Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou Recruiting
Rennes cedex 9, France
Contact: Anna Bernard    +33299284321    anna.bernard@chu-rennes.fr   
Principal Investigator: Sophie De Guibert, MD         
Sponsors and Collaborators
Pharmacyclics
Janssen Research & Development, LLC
Investigators
Study Director: Darrin Beaupre, MD, PhD Pharmacyclics
  More Information

No publications provided

Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01980628     History of Changes
Other Study ID Numbers: PCYC-1121-CA
Study First Received: October 29, 2013
Last Updated: July 30, 2014
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: National Agency for the Safety of Medicine and Health Products

Keywords provided by Pharmacyclics:
MZL
NHL
SMZL
NMZL
MALT

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 27, 2014