Multicenter Phase II Single Arm Open-label Study on the Feasibility, Safety and Efficacy of Combination of CHOP-21 Supplemented With Obinutuzumab and Ibrutinib in Untreated Young High Risk Diffuse Large B-cell Lymphoma (DLBCL) Patients.
Overview
- Phase
- Phase 2
- Intervention
- Obinutuzumab
- Conditions
- Lymphoma, B-Cell
- Sponsor
- Fondazione Italiana Linfomi - ETS
- Enrollment
- 1
- Locations
- 29
- Primary Endpoint
- The safety of G-CHOP-21 in combination with Ibrutinib in terms of proportion of patients experiencing grade 3 or greater extra-hematologic toxicity or treatment interruption for safety reasons or any toxic death during the 6 cycles of treatment
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a prospective, multicenter, single arm, phase II trial in young patients (18-60 years) with poor-prognosis (aaIPI 2 or 3) newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL).
Aim of the study is to assess the efficacy and the safety of G-CHOP in combination with ibrutinib.
Detailed Description
This is a prospective, multicenter, single arm, phase II trial in young patients (18-60 years) with poor-prognosis (age-adjusted International Prognostic Index, aaIPI, 2 or 3) newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Patient will receive 6 courses of G-CHOP21 (Obimutizumab- cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone) followed by 2 doses of Obinutuzumab supplemented with Ibrutinib. Duration of treatment will be 5 months plus 4-5 weeks for response evaluation. During the study, disease status will be evaluated after the 4th cycle by computed tomography (CT) scan, and after end of treatment by imaging test (18FDG-PET \[positron emission tomography\] and CT scan). Patients will be recruited over 2 years and followed for a minimum of 2 years after the end of the treatment phase.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified (NOS)
- •Previously untreated disease
- •Age 18-60
- •Age adjusted IPI=2-3
- •Ann Arbor stage II-IV disease
- •Measurable disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions
- •Normal blood count as defined as: absolute neutrophil count ≥1.0 × 109/L independent of growth factor support, platelet count ≥ 100,000/mm3 or ≥50,000/mm3 if bone marrow (BM) involvement independent of transfusion support in either situation
- •Normal organ functions defined as: creatinine ≤2 times the upper limit of normal (ULN) or estimated Glomerular Filtration Rate (Cockroft- Gault) ≥40 ml/min/1.73m2, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3× the ULN; total bilirubin ≤ 1.5 × the ULN unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic origin: patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 × the ULN; International normalized ratio (INR) \< 1.5 × the ULN in the absence of therapeutic anticoagulation; partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) \< 1.5 × the ULN in the absence of a lupus anticoagulant"
- •Patients with occult or prior hepatitis B infection (defined as HBsAg negative, anti-HBs positive and /or anti-HBc positive) may be included if hepatitis B virus (HBV) DNA is undetectable. These patients must be willing to undergo bi-monthly DNA testing and they should receive prophylaxis with Lamivudine
- •No active hepatitis C virus (HCV) infection
Exclusion Criteria
- •Any Other histologies than Diffuse Large B- Cell Lymphoma (DLBCL): composite or transformed disease and patients with follicular lymphoma IIIB
- •Primary mediastinal lymphoma (PMBL)
- •Known central nervous system lymphoma
- •Any prior lymphoma therapy
- •Contraindication to any drug in the chemotherapy regimen
- •Left ventricular ejection fraction (LVEF) \< 50%
- •Neuropathy ≥ grade 2
- •Seropositive for or active viral infection with HBV
- •HBsAg positive
- •HBsAg negative, anti-HBs positive and /or anti-HBc positive with detectable viral DNA
Arms & Interventions
G CHOP 21 + Ibrutinib
Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib.
Intervention: Obinutuzumab
G CHOP 21 + Ibrutinib
Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib.
Intervention: Ibrutinib
G CHOP 21 + Ibrutinib
Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib.
Intervention: CHOP
Outcomes
Primary Outcomes
The safety of G-CHOP-21 in combination with Ibrutinib in terms of proportion of patients experiencing grade 3 or greater extra-hematologic toxicity or treatment interruption for safety reasons or any toxic death during the 6 cycles of treatment
Time Frame: 5 months of treatment
The efficacy of G-CHOP-21 in combination with Ibrutinib in terms of 2-yrs PFS (progression-free survival)
Time Frame: 2 years
Secondary Outcomes
- Overall Survival (OS)(2 years)
- Overall Response Rate (ORR)(6 months)
- Complete Remission (CR) Rate(6 months)
- The Duration Of Response (DOR) after the end of treatment(2 years)