Phase II Randomized Clinical Trial to Evaluate the Efficacy of the Addition of Polatuzumab Vedotin to Standard Chemotherapy R-DHAP (POLA-R-DHAP) as Induction Pre-transplantation Therapy in Patients With Diffuse Large B-Cell Lymphoma Refractory/Relapsed After First Line Treatment.
Overview
- Phase
- Phase 2
- Intervention
- R-DHAP
- Conditions
- Diffuse Large B Cell Lymphoma Refractory
- Sponsor
- Fondazione Italiana Linfomi - ETS
- Locations
- 37
- Primary Endpoint
- Progression free survival (PFS)
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus Polatuzumab Vedotin as induction treatment plus autologous transplant.
Detailed Description
Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus Polatuzumab Vedotin as induction treatment. PET-CT scan performed after induction be centrally review for disease response. Responding patients (CR) after induction will be addressed to receive Autologous Stem Cells Transplantation (ASCT) consolidation as per local guidelines. Patients achieving PR can proceed with ASCT or with a 3rd-line treatment, according to the physician judgment. Patients in SD/PD will be diverted to salvage strategies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically documented diagnosis of Diffuse Large B-Cell Lymphoma Not otherwise specified (DLBCL-NOS) as defined in the 2022 edition of the World Health Organization (WHO) classification; are also admitted documented diagnosis of:
- •T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL)
- •Epstein-barr virus (EBV)-associated DLBCL
- •Double-hit and triple-hit high grade B-cell lymphomas (HGBL DH/TH)
- •High-grade B-cell lymphoma, NOS (HGBL)
- •Transformed FL not previously untreated
- •Follicular large B-cell lymphoma (FLBL, former follicular 3b)
- •Known availability of biopsy material (at relapse/refractory or previous most recent). Re-biopsy highly encouraged even if not mandatory. Central pathology review required, but not mandatory for registration and treatment start;
- •Relapse or refractoriness after the first line R-chemo (R-CHOP o similar). Previous treatment with polatuzumab containing regimen is allowed as per clinician judgment;
- •CAR-T not indicated or unavailable;
Exclusion Criteria
- •Any histology other than DLBCL
- •Primary mediastinal lymphoma (PMBCL)
- •Known central nervous system lymphoma
- •Known history of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
- •Contraindication to any drug in the chemotherapy regimen
- •Left ventricular ejection fraction (LVEF) \< 50%
- •Neuropathy ≥ grade 2
- •Subject is:
- •Seropositive for hepatitis B, defined by a positive test for hepatitis B surface antigen \[HBsAg\]. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (HBsAb positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
- •Known to be seropositive for hepatitis C. EXCEPTION: Patients with presence of HCV antibody, but PCR negative for HCV-RNA are eligible
Arms & Interventions
R-DHAP
R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)
Intervention: R-DHAP
Pola-R-DHAP
Pola-R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)
Intervention: Pola-R-DHAP
Outcomes
Primary Outcomes
Progression free survival (PFS)
Time Frame: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)
Time between the randomization to first documentation of recurrence, progression or death from any cause
Secondary Outcomes
- Event-Free Survival (EFS)(From treatment start up to 30 months (6 months treatment period and 24 months of follow-up))
- Overall response rate (ORR)(From treatment start up to end of treatment evaluation (about 6 months))
- Overall Survival (OS)(From treatment start up to 30 months (6 months treatment period and 24 months of follow-up))
- Adequate stem cells mobilization(From beginning of 2nd cycle to end of induction treatment evaluation (about 2 months))
- Complete response rate (CRR)(From treatment start up to end of treatment evaluation (about 6 months))
- Incidence and severity of AEs(From start to end of induction treatment evaluation (about 3 months))
- Autologous consolidation feasibility(At time of end of treatment assessment (up to 6 months from treatment begin))