Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma MedDRA version: 14.1 Level: LLT Classification code 10012820 Term: Diffuse large B-cell lymphoma NOS System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - No prior treatment for diffuse B-cell lymphoma (DLBCL) - Histologically-confirmed nongerminal center B-cell subtype DLBCL - Stage II (not candidates for local x-ray therapy), III, or IV disease by the Ann Arbor Classification - At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma - Revised International Prognostic Index score of >=1 - Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2 - Hematology and biochemical laboratory values within protocol defined parameters within 14 days prior to random assignment and at baseline - Left ventricular ejection fraction within institutional normal limits, as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan - Agrees to protocol-defined use of effective contraception (for women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose of study drug, whichever is later; for men, these restrictions apply for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later) - Men must agree to not donate sperm during and after the study for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later - Women of childbearing potential must have a negative serum 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) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: - Major surgery within 4 weeks of random assignment - Known central nervous system or primary mediastinal lymphoma - Prior history of indolent lymphoma - Diagnosed or treated for malignancy other than DLBCL, 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 carcinoma in situ without evidence of disease - 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 CYP3A4/5 inhibitors - Prior anthracycline use >=150 mg/m2 - 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 or active hepatitis C virus or active hepatitis B virus infection 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 ibrutinib capsules, or put the study outcomes at undue risk
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate if the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) prolongs event-free survival (EFS) compared with R-CHOP alone in subjects with newly diagnosed non-GCB DLBCL.;Secondary Objective: The secondary objectives are to: ? Evaluate PFS ? Evaluate overall survival ? Evaluate CR rate ? Evaluate patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) ? Evaluate the treatment benefit of ibrutinib in subjects with the ABC subtype based on GEP ? Characterize the pharmacokinetics of ibrutinib and to explore the potential relationships between ibrutinib metrics of exposure with relevant clinical or biomarker information ? Evaluate the safety of ibrutinib when combined with R-CHOP The exploratory objectives are to: ? Evaluate patient-reported outcomes (PRO), related to well-being and general health status, utilizing the FACT-Lym and EuroQol questionnaire (EQ-5D-5L) ? Explore the relationship between relevant biomarkers (eg, GEP, gene mutations) with clinical outcomes and mechanism of resistance;Primary end point(s): Event-free survival;Timepoint(s) of evaluation of this end point: Up to disease progression, relapse from complete response, initiation of subsequent systemic antilymphoma therapy after completion of at least 6 cycles of R-CHOP therapy, or death, whichever occurs first, up to Year 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-free survival - Overall survival - Complete response rate - Time to worsening symptoms in the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) - Oral plasma clearance of ibrutinib - Oral volume of distribution at steady state of ibrutinib - Area under the plasma concentration-time curve of ibrutinib - Minimum observed plasma concentration of ibrutinib - Number of participants affected by an adverse event;Timepoint(s) of evaluation of this end point: - Up to disease progression, relapse from complete response, or death, whichever occurs first, up to Year 7 - Up to the date of the participants death, up to Year 7 - Up to completion of chemotherapy treatment, up to Year 7 - Up to the start date of the worsening of patient symptoms, up to Year 7 - Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 - Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 - Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 - Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 - Up to 30 days after the last dose of study medication | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed