A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination with Bendamustine and Rituximab (BR) in Subjects With Newly Diagnosed Mantle Cell Lymphoma
- Conditions
- Mantel cell lymphome or Non-Hodgekin lymphoma10025320
- Registration Number
- NL-OMON52974
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
- Diagnosis of mantle cell lymphoma (MCL) reviewed and approved by central
laboratory: diagnosis must include morphology and expression of either cyclin
D1 in association with other relevant markers (eg, CD19, CD20, PAX5) and CD5 or
evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ
hybridization (FISH), or polymerase chain reaction (PCR), - Clinical Stage II,
III, or IV by Ann Arbor Classification, - At least 1 measurable site of disease
according to Revised Response Criteria for Malignant Lymphoma, - No prior
therapies for MCL, - Eastern Cooperative Oncology Group (ECOG) performance
status grade 0 or 1, - Hematology and biochemical laboratory values within
protocol-defined limits, - Agrees to protocol-defined use of effective
contraception, - Negative blood or urine pregnancy test at screening
- Major surgery within 4 weeks of random assignment, - Known central nervous
system lymphoma, - Diagnosed or treated for malignancy other than MCL, except:
malignancy treated with curative intent and with no known active disease
present for >=3 years before random assignment; adequately treated
non-melanoma skin cancer or lentigo maligna without evidence of disease;
adequately treated cervical carcinoma in situ without evidence of disease, -
Patients for whom the goal of therapy is tumor debulking prior to stem cell
transplant, - History of stroke or intracranial hemorrhage within 6 months
prior to random assignment, - Requires anticoagulation with warfarin or
equivalent vitamin K antagonists, - Requires treatment with strong CYP3A
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, - Vaccinated with live, attenuated
vaccines within 4 weeks of random assignment, - Known history of human
immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B
virus infection or any uncontrolled active systemic infection requiring
intravenous antibiotics, - 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 ibrutinib
capsules, or put the study outcomes at undue risk
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Objective<br /><br>The primary objective of this study is to evaluate whether the addition of<br /><br>ibrutinib to bendamustine and rituximab will result in prolongation of PFS in<br /><br>subjects with newly diagnosed MCL who are 65 years of age or older.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives are:<br /><br>• To evaluate overall survival<br /><br>• To evaluate the CR rate and overall response rate (CR+PR)<br /><br>• To evaluate patient-reported lymphoma symptoms and concerns as measured by<br /><br>the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma<br /><br>(FACT-Lym)<br /><br>• To evaluate the minimal residual disease (MRD) negative rate<br /><br>• To evaluate duration of response<br /><br>• To evaluate time-to-next treatment (TTNT)<br /><br>• To evaluate the safety of ibrutinib when combined with BR<br /><br>• To characterize the pharmacokinetics of ibrutinib and explore the potential<br /><br>relationships between ibrutinib metrics of exposure with relevant clinical,<br /><br>pharmacodynamic, or biomarker information</p><br>