Improvement of Outcome and Reduction of Toxicity in Elderly Patients With CD20+ Aggressive B-Cell Lymphoma by an Optimised Schedule of the Monoclonal Antibody Rituximab, Substitution of Conventional by Liposomal Vincristine, and FDG-PET Based Reduction of Therapy.
Primary objective of study:
"OPTIMAL>60 Less Favourable" Patients with less favourable prognosis:
1. To test whether progression-free survival (PFS) can be improved by substituting
conventional by liposomal vincristine;
2. To test whether PFS can be improved by 12 optimised applications instead of 8 2-week
applications of rituximab.
"OPTIMAL>60 Favourable": Patients with favourable pro-gnosis:
3. Comparison of neurotoxicity of conventional and liposomal vincristine;
4. Determination of PFS for the treatment strategy of reducing treatment in patients with
negative FDG-PET after 4 x R-CHOP/CHLIP-14 (PET-4) and comparison with the
corresponding patient population in RICOVER-60.
"OPTIMAL>60 Favourable" and "OPTIMAL>60 Less Favourable":
5. Comparison of the prognostic value of a pre-treatment FDG-PET (PET-0) with conventional
6. Comparison of the FDG-PET-based individualised treatment strategy in OPTIMAL>60 with
the fixed (pre-defined) treatment strategy in RICOVER>60.
7. Estimation of the vincristine-related neurotoxicity ("OPTIMAL>60 Less Favourable only,
since vincristine related neurotoxicity is primary objective of the study in favourable
patients) and other toxicities (all patients).
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
"OPTIMAL>60 Less Favourable": To test the effects of substitution of conventional by liposomal vincristine and of a 2-week applications of 8x rituximab by an optimised application of 12 x rituximab stratified log rank tests will be performed for each question (stratified for IPI-factors). Proportional hazard models will be used to investigate treatment interaction and to obtain estimates for the single treatment effects (HR) adjusting for the IPI-factors. "OPTIMAL>60 Favourable" Grade of neurotoxicity will be estimated and indicated with a 95% confidence interval (CI) separated to each type of vincristine. To investigate the 3-year PFS with 95% CI the Kaplan-Meier estimator will be used.
Michael G. Pfreundschuh, Professor
Saarland University, Saarland University Hospital
Germany: Ethics Commission