Activated-B-Cell Lymphoma (ABC)-DLBCL at intermediate-high and high risk (IPI =2) 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 -CAPSULE RIGIDE -USO ORALE - FLACONE (HDPE) - 1 FLACONE (120 CAPSULE RIGIDE)
Product Name: Ibrutinib
Product Code: IMP1
Pharmaceutical Form: Capsule, hard
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed DLBCL not otherwise specified (NOS) • ABC type defined by Lymph2Cx on the NanoString platform. Note: A formalin fixed paraffin embedded lymph node or tumor biopsy specimen must be submitted to Central Pathology for review during the Screening Period. The specimen must have been acquired by a surgical incision or excision biopsy or from a core needle biopsy • Previously untreated disease • Age = 18 and 6 months 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects
Exclusion criteria
Exclusion criteria: • DLBCL including High grade B-cell Lymphomas, both with double hit and NOS according to the 2017 Revised WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues • GCB-DLBCL after centralized COO profiling • Any other histologies than DLBCL: composite or transformed disease, patients with follicular lymphoma IIIB and large B-cell lymphoma with IRF4 rearrangement. • Primary mediastinal lymphoma (PMBL) • Known central nervous system lymphoma • Primary testicular lymphoma • Any prior lymphoma therapy • Contraindication to any drug in the chemotherapy regimen • Left ventricular ejection fraction (LVEF) 1.5 × the ULN: patients with documented Gilbert disease may be enrolled if total bilirubin is = 3.0 × the ULN; INR > 1.5 × the ULN in the absence of therapeutic anticoagulation; PTT or aPTT > 1.5 × the ULN in the absence of a lupus anticoagulant” • History of stroke or intracranial hemorrhage within the past 6 months. • Requires anticoagulation with warfarin or equivalent vitamin K antagonists • Requires treatment with strong CYP3A inhibitors • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances • 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. • Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics • Major surgical intervention prior 4 weeks to enrollment if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment • Prior malignancies other than lymphoma in the last 5 years with exception of currently treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix • 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. • If female, the patient is pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the 2-years PFS of R-CHOP21 in combination with ibrutinib followed by maintenance in untreated patients with ABC-DLBCL, at IPI = 2.;Secondary Objective: - To evaluate the efficacy in terms of OS; - To evaluate the Complete Response (CR) rate and Overall Response Rate (ORR) (Lugano 2014); - To evaluate the duration of response (DOR) after the end of treatment. - To evaluate the rate of conversion in CR with ibrutinib maintenance for patients in PR after the EOI. - To evaluate the safety of R-CHOP in combination with ibrutinib;Primary end point(s): Progression-free survival (PFS) of the high/high-intermediate risk patients from date of enrolment;Timepoint(s) of evaluation of this end point: Time between the date of enrolment and the date of disease progression, relapse or death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS); Complete response and Overall Response (CR+PR) rate; Duration of response (DOR); The rate of complete remission (CRR) before and after ibrutinib maintenance; Rate of conversion in CR with ibrutinib after 3 months of maintenance for patients in PR after the EOI; Toxicity: all grade of toxicity and severe, life- threatening, fatal (grade >=3) and/or serious adverse events will be defined according to CTCAE, version 4.03;Timepoint(s) of evaluation of this end point: Time between the date of enrolment and the date of death from any cause; End of induction; From the date when criteria for response are met (CR or PR) until the date of progression or relapse. Patients without relapse or progression or death from other causes will be censored at their last assessment date.; End of induction (EOI) and End of treatment (EOT); End of treatment (after maintenance); Throughout the study | — |
Countries
Italy
Contacts
Public ContactUffici Studi FIL
Fondazione Italiana Linfomi Onlus
Outcome results
None listed