Mantle Cell Lymphoma MedDRA version: 20.0 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 520
Exclusion criteria
Exclusion criteria: - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objectives are: ? To evaluate overall survival ? To evaluate the CR rate and overall response rate (CR+PR) ? To evaluate patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) ? To evaluate the minimal residual disease (MRD) negative rate ? To evaluate duration of response ? To evaluate time-to-next treatment (TTNT) ? To evaluate the safety of ibrutinib when combined with BR ? To characterize the pharmacokinetics of ibrutinib and explore the potential relationships between ibrutinib metrics of exposure with relevant clinical, pharmacodynamic, or biomarker information ;Primary end point(s): Progression-free survival;Timepoint(s) of evaluation of this end point: Up to the end-of-study visit until 265 progression-free survival events have been observed (up to 7 years after the last patient is randomized);Main Objective: The primary objective of this study is to evaluate whether the addition of ibrutinib to bendamustine and rituximab will result in prolongation of progression-free survival (PFS) in subjects with newly diagnosed MCL who are 65 years of age or older. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Overall survival Time frame = up to the end-of-study visit until 60% of all enrolled patients have died (up to 7 years after the last patient is randomized) 2) Overall response rate Time frame = up to the end-of-study visit up to 7 years after the last patient is randomized 3) Number of participants with change in Lym subscale scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT Lym) Time frame = screening, Day 1 of the first 6 cycles, then every 12 weeks in the first 12 months, thereafter every 16 weeks up to 7 years after the last patient is randomized 4) Minimal residual disease negative rate Time frame = for participants with complete response, every 12 weeks in the first 12 months, thereafter every 16 weeks and at disease progression or up to the end-of-study visit (up to 7 years after the last patient is randomized) 5) Duration of response Time frame = up to the end-of-study visit up to 7 years after the last patient is randomized 6) Time-to-next treatment Time frame = up to the end-of-study visit up to 7 years after the last patient is randomized 7) Number of participants affected by an adverse event Time frame = up to 30 days after the last dose of study treatment 8) Oral plasma clearance of ibrutinib as derived from population pharmacokinetics Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1 and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose 9) Oral volume of distribution at steady state of ibrutinib as derived from population pharmacokinetics Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1 and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose 10) Area under the concentration curve of ibrutinib as derived from population pharmacokinetics Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1 and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose 11) Minimum observed plasma concentration of ibrut | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Czech Republic, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Portugal, Russian Federation, Singapore, Slovakia, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed