diffuse large B-cell lymphoma MedDRA version: 21.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: IMBRUVICA 140 mg hard capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: IBRUTINIB
CAS Number: 936563-96-1
Other descriptive name: IBRUTINIB
Concentration unit: mg milligram(
Sponsors
Universitätsklinikum Münster
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study. 2. Age between 18-60 years 3. Risk score 2 or 3 according to aaIPI 4. Histology: Primary diagnosis of - DLBCL (NOS) or - High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements or - High-grade B-cell lymphoma, NOS 5. Performance status: ECOG 0-3 6. Stage: all stages according Ann Arbor 7. ANC: > 1000 cells/microliter (independent of growth factor support) 8. Platelet count = 100.000/mm3 or = 50.000/mm3 if bone marrow involvement independent of transfusion support in either situation. 9. ALT and AST: =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Vaccinated with live, attenuated vaccines within 4 weeks of inclusion. 2. Major surgery within 4 weeks of inclusion. 3. Any prior lymphoma-directed therapy (except pre-phase treatment). 4. Known central nervous system involvement. 5. Diagnosed or treated for malignancy other than DLBCL, in particular any other (indolent) lymphoma. 6. 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 or 4 cardiac disease as defined by the New York Heart Association Functional classification. 7. Bone marrow involvement > 25% 8. History of stroke or intracranial hemorrhage within six months of inclusion. 9. Requires anticoagulation with warfarin or equivalent vitamin K antagonist. 10. Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring IV antibiotics. 11. Requires treatment with strong CYP3A inhibitors. 12. Use of preparations containing St. John’s Wort. 13. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk. 14. Concurrent treatment with other investigational agent or X-ray therapy. 15. Previous chemo- or radiotherapy for any other malignancy, in particular indolent lymphoma. 16. Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator’s opinion, compromises the patient’s ability to understand the patient information, to give informed consent or to comply with the study protocol. 17. Participation in another interventional clinical trial during this trial. There may be exceptions at the discretion of the coordinating investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to estimate the 2-year progression-free survival (PFS) achieved with ibrutinib in combination with immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone (R-CHOEP) in newly diagnosed, younger patients (age 18-60 years) with diffuse large B-cell lymphoma (DLBCL) and age-adjusted International Prognostic Index (aaIPI) 2 or 3.;Secondary Objective: The secondary objectives for efficacy are to evaluate overall survival (OS), event-free survival (EFS), rate of complete remission (CR), rate of partial remission (PR), overall response rate (ORR) (CR+PR), progression rate, relapse rate and the duration of response. Other secondary objectives of the trial are to assess the • rate of treatment-related deaths, • feasibility, safety, toxicity, and protocol adherence of ibrutinib when combined with R-CHOEP and • outcome according to biological parameters of the tumor. A preplanned additional analysis is to compare patients from this study with patients from the previous R-MegaCHOEP phase III trial (Schmitz et al., Lancet Oncol 2012).;Primary end point(s): 2-year PFS with 95% confidence intervals (CI) in 40 patients without CNS disease.;Timepoint(s) of evaluation of this end point: In the course of therapy and follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints for efficacy: OS, EFS, CR rate, PR rate, ORR, progression rate, relapse rate, duration of response. Other secondary endpoints: AEs, SAEs, treatment-related deaths, Secondary malignancies, Number and duration of therapy cycles, Cumulative doses of cyclophosphamide, doxorubicin, vincristine, etoposide, rituximab and ibrutinib, outcome according to biological parameters. Furthermore, PFS achieved in this trial will be compared to historical controls (DLBCL patients with aaIPI 2 or 3 treated with R-CHOEP-14 within R-MegaCHOEP phase III trial; Schmitz et al. Lancet Oncology 2012).;Timepoint(s) of evaluation of this end point: In the course of therapy and follow-up. | — |
Countries
Germany
Contacts
Public ContactCentral study office
Universitätsklinikum Münster
Outcome results
None listed