- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01779791
A Study of PCI-32765 (Ibrutinib) in Patients With Refractory Follicular Lymphoma
July 14, 2017 updated by: Janssen Research & Development, LLC
An Open-Label, Multicenter, Single-Arm, Phase 2 Study of PCI-32765 (Ibrutinib) in Subjects With Refractory Follicular Lymphoma
The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib) administered to patients with chemoimmunotherapy-resistant follicular lymphoma (FL).
Study Overview
Detailed Description
This is an open-label (identity of assigned study drug will be known) study of PCI-32765 (ibrutinib) in approximately 110 patients with chemoimmunotherapy-resistant FL whose disease has relapsed from at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen.
Each patient must have resistant disease to the last therapy (defined as progression of disease [PD] during or within 12 months of the last dose of chemotherapy in a CD20 antibody combination chemotherapy regimen).
The study will include the following phases: screening (up to 30 days prior to the first dose of study drug), treatment (until PD or unacceptable toxicity), and posttreatment follow-up (until death, lost to follow up, withdrawal of consent, or study end [defined as 2 years after the last patient is enrolled]).
Patients will receive 560 mg of PCI-32765 by mouth once daily on a 21-day cycle.
Treatment will be continuous (without interruption) and self-administered at home.
The treatment phase will extend from administration of the first dose of study medication until PD or unacceptable toxicity.
If a patient who had radiological evidence of PD is clinically stable or improving or exhibiting signs of tumor flare without confirmation of PD by PET or biopsy, they may continue treatment with ibrutinib upon request by the investigator and approval by the sponsor.
Posttreatment follow-up will extend from the end of treatment until death, lost to follow up, withdrawal of consent, or study end.
Every patient, except for those who explicitly withdraw consent from further site contact, will be followed for survival status until the study ends.
In addition, data on subsequent antineoplastic therapy will also be collected.
Serial pharmacokinetic samples will be collected and efficacy and safety will be monitored throughout the study.
A separate assessment of pharmacokinetics is planned for patients who receive a strong or moderate CYP3A4/5 inhibitor while receiving treatment with ibrutinib.
For patients who have already discontinued ibrutinib due to PD, have taken no other anticancer therapy, and now have a radiologically documented delayed response, resumption of ibrutinib is permitted on a case-by-case basis, upon request by the investigator and approval of the sponsor.
Study Type
Interventional
Enrollment (Actual)
110
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Adelaide, Australia
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Concord, Australia
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Melbourne, Australia
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Milton, Australia
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Prahran, Australia
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Courrière, Belgium
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Gent, Belgium
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Leuven, Belgium
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Creteil, France
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Nice Cedex 2, France
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Nimes Cedex 9, France
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Paris, France
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Pessac, France
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Pierre Benite, France
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Rennes, France
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Heidelberg, Germany
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Köln, Germany
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Mainz, Germany
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Ulm, Germany
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Krakow, Poland
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Warszawa, Poland
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Wroclaw, Poland
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Ekaterinburg, Russian Federation
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Moscow N/A, Russian Federation
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Nizhny Novgorod, Russian Federation
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St-Petersburg, Russian Federation
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Volgograd, Russian Federation
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Barcelona, Spain
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Marbella, Spain
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Salamanca, Spain
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Liverpool, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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Southampton, United Kingdom
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California
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Los Angeles, California, United States
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Stanford, California, United States
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District of Columbia
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Washington, D.C., District of Columbia, United States
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Georgia
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Atlanta, Georgia, United States
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Illinois
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Chicago, Illinois, United States
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Kansas
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Westwood, Kansas, United States
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Kentucky
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Lexington, Kentucky, United States
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Louisville, Kentucky, United States
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Maryland
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Baltimore, Maryland, United States
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Michigan
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Detroit, Michigan, United States
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New Jersey
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Hackensack, New Jersey, United States
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New Brunswick, New Jersey, United States
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New York
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New York, New York, United States
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North Carolina
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Greenville, North Carolina, United States
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Oregon
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Portland, Oregon, United States
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Pennsylvania
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Texas
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Houston, Texas, United States
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Vermont
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Burlington, Vermont, United States
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Washington
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Seattle, Washington, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologic proof of Grade 1, 2, or 3a follicular lymphoma (FL) without clinical or pathological evidence of transformation
- Previously treated with at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen; last prior line of therapy includes an anti CD20 monoclonal antibody-containing chemotherapy regimen (separate lines of therapy are defined as different regimens that are either separated by disease progression, refractory disease, or relapsed disease)
- Resistant disease to the last therapy, defined as progression of disease during or within 12 months of the last dose of chemotherapy in a CD20 antibody combination chemotherapy regimen
- At least 1 measurable site of disease according to International Working Group Revised Response Criteria for Malignant Lymphoma
- Eastern Cooperative Oncology Group performance status grade 0 or 1
- Hematology and biochemical laboratory values must be within protocol-defined parameters within 7 days prior to enrollment
- Agrees to protocol-defined use of effective contraception
- Women of childbearing potential must have a negative serum or urine pregnancy test at screening
Exclusion Criteria:
- Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug
- Prior treatment with PCI-32765 or other Bruton's tyrosine kinase inhibitors (patients who progressed or became refractory while on treatment with PI3K inhibitors are excluded)
- Concurrent enrollment in another therapeutic investigational clinical treatment study
- Received a prior allogeneic hematopoietic stem cell transplant (prior autologous hematopoietic stem cell transplant is allowed)
- Known central nervous system lymphoma
- History of prior malignancy (except malignancy treated with curative intent and with no known active disease present for >=3 years before enrollment, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, or adequately treated cervical carcinoma in situ without evidence of disease)
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists
- Requires treatment with strong cytochrome P450 (CYP)3A4/5 inhibitors
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C or active infection with Hepatitis B or any uncontrolled active systemic infection requiring intravenous antibiotics
- Women who are pregnant or breastfeeding
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: PCI-32765 (Ibrutinib)
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560 mg capsules administered orally once daily, continuously on a 21-day cycle until progressive disease.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Overall response rate
Time Frame: Up to 2 years after the last patient is enrolled
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Up to 2 years after the last patient is enrolled
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Duration of response
Time Frame: Every 12 weeks during the first 96 weeks, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled)
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Every 12 weeks during the first 96 weeks, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled)
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Progression-free survival
Time Frame: Up to progressive disease, death, lost to follow-up, withdrawal of consent, or study end (up to 2 years after the last patient is enrolled)
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Up to progressive disease, death, lost to follow-up, withdrawal of consent, or study end (up to 2 years after the last patient is enrolled)
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Overall survival
Time Frame: Up to death, lost to follow-up, withdrawal of consent, or study end (up to 2 years after the last patient is enrolled)
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Up to death, lost to follow-up, withdrawal of consent, or study end (up to 2 years after the last patient is enrolled)
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Time to response
Time Frame: Every 12 weeks during the first 96 weeks, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled)
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Every 12 weeks during the first 96 weeks, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled)
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Number of patients experiencing resolution of lymphoma-related B symptoms
Time Frame: Day 1 of every cycle during the first 12 months, thereafter every other cycle (up to 2 years after the last patient is enrolled)
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Day 1 of every cycle during the first 12 months, thereafter every other cycle (up to 2 years after the last patient is enrolled)
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Number of patients identified with blood biomarkers that alter B-cell receptor signaling or activate alternative signaling pathways
Time Frame: Day 1 of Cycles 1-3, and time of disease progression, or at end-of treatment visit for patients who discontinue treatment without disease progression
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Day 1 of Cycles 1-3, and time of disease progression, or at end-of treatment visit for patients who discontinue treatment without disease progression
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Minimum plasma concentration of PCI-32765
Time Frame: Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Oral plasma clearance of PCI-32765
Time Frame: Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Oral volume of distribution at steady state of PCI-32765
Time Frame: Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Area under the plasma-concentration time curve of PCI-32765
Time Frame: Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
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Number of participants affected by an adverse event
Time Frame: Up to 30 days after the last dose of study medication
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Up to 30 days after the last dose of study medication
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Balasubramanian S, Hodkinson B, Schuster SJ, Fowler NH, Trotman J, Hess G, Cheson BD, Schaffer M, Sun S, Deshpande S, Vermeulen J, Salles G, Gopal AK. Identification of a genetic signature enriching for response to ibrutinib in relapsed/refractory follicular lymphoma in the DAWN phase 2 trial. Cancer Med. 2022 Jan;11(1):61-73. doi: 10.1002/cam4.4422. Epub 2021 Nov 17.
- Gopal AK, Schuster SJ, Fowler NH, Trotman J, Hess G, Hou JZ, Yacoub A, Lill M, Martin P, Vitolo U, Spencer A, Radford J, Jurczak W, Morton J, Caballero D, Deshpande S, Gartenberg GJ, Wang SS, Damle RN, Schaffer M, Balasubramanian S, Vermeulen J, Cheson BD, Salles G. Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study. J Clin Oncol. 2018 Aug 10;36(23):2405-2412. doi: 10.1200/JCO.2017.76.8853. Epub 2018 May 31.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 17, 2013
Primary Completion (Actual)
May 18, 2016
Study Completion (Actual)
May 18, 2016
Study Registration Dates
First Submitted
January 25, 2013
First Submitted That Met QC Criteria
January 28, 2013
First Posted (Estimate)
January 30, 2013
Study Record Updates
Last Update Posted (Actual)
July 18, 2017
Last Update Submitted That Met QC Criteria
July 14, 2017
Last Verified
July 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR100956
- 2012-004097-26 (EudraCT Number)
- PCI-32765FLR2002 (Other Identifier: Janssen Research & Development, LLC)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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