Phase II Multicenter Single Arm Study to Evaluate the Efficacy and Safety of Ibrutinib in Combination to Rituximab-CHOP Followed by Ibrutinib Maintenance in Untreated Patients With Activated-B-Cell (ABC)-DLBCL at Intermediate-high and High Risk (IPI ≥2)
Overview
- Phase
- Phase 2
- Intervention
- Ibrutinib
- Conditions
- DLBCL
- Sponsor
- Fondazione Italiana Linfomi - ETS
- Enrollment
- 75
- Locations
- 39
- Primary Endpoint
- Progression-free survival (PFS) (1st time point of assessment)
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a prospective, multicenter, single arm, phase II trial in patients with ≥ 18 and <65 years with poor-prognosis (IPI ≥ 2) and newly diagnosed ABC-DLBCL.
Aim of the study is to assess the efficacy and the safety of R-CHOP in combination with ibrutinib for 6 cycles followed by ibrutinib maintenance for 18 months in ABC-DLBCL patients achieving at least a PR after the induction phase
Detailed Description
Step 1 - Screening phase If central review will confirm and define the diagnosis of ABC-DLBCL according the COO, eligible patients will have to sign an additional informed consent prior to receive the study subsequent treatment. Step 2 - study treatment phases Induction phase: 5 courses of R-CHOP every 21 days combined with ibrutinib (560 mg/day, continuously). Maintenance phase: patients achieving a CR or a PR after 5 courses of RI-CHOP21 will enter the maintenance phase with ibrutinib (560 mg/day, continuously) for 18 months. Radiotherapy could be delivered as consolidation treatment at the end of R-chemotherapy, according to Institution local clinical practice, in patients with focal PET positive residual disease and to bone extranodal lesions or scrotum, if testicular involvement irrespective of initial tumor diameter.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Ibrutinib+R-CHOP
Screening phase for selection of Activated-B-Cell (ABC)-DLBCL Induction phase: R-CHOP21 x 5 cycles in combination with ibrutinib Maintenance phase: maintenance with Ibrutinib for 18 months for patients responding to the induction phase (CR or PR)
Intervention: Ibrutinib
Outcomes
Primary Outcomes
Progression-free survival (PFS) (1st time point of assessment)
Time Frame: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (24 months)
PFS of the high/high-intermediate risk patients from date of enrolment
Progression-free survival (PFS) (2nd time point of assessment)
Time Frame: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (36 months)
PFS of the high/high-intermediate risk patients from date of enrolment
Progression-free survival (PFS) (3dr time point of assessment)
Time Frame: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (48 months)
PFS of the high/high-intermediate risk patients from date of enrolment
Secondary Outcomes
- Complete response and Overall Response (CR+PR) rate at the end of induction(End of induction (EOI) (4 months))
- Overall Survival (OS)(Time between the date of enrolment and the date of death from any cause (24, 36 and 48 months).)
- Complete remission (CRR) after ibrutinib maintenance(End of treatment (EOT) (up to 24 months))
- Duration of response (DOR)(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 (24 months from response date))
- Event Free Survival (EFS)(From the date of enrolment to the date of disease progression, relapse from CR, initiation of subsequent systemic anti-lymphoma therapy after the least 6 cycles of RI-CHOP (each cycle is 21 days), or death whichever occurs first (24, 36 and 48 months))