study of tafasitamab and lenalinomide associated to rituximab in frontline diffuse large b-cell lymphoma patients of 80 y/o or older

Conditions: DLBCL

Summary: this study evaluate the efficacy of tafasitamab and lenalinomide associated to rituximab in elderly patients with frontline diffuse large b-cell lymphoma as assessed by the overall response rate (orr) after 3 cycles of treatment according to lugano response criteria.

this study is an open-label, multi-centric, phase ii study designed to evaluate the efficacy of tafasitamab and lenalinomide associated to rituximab in elderly patients with frontline diffuse large b-cell lymphoma as assessed by the overall response rate (orr) after 3 cycles of treatment according to lugano response criteria. after a screening phase, eligible patients will be enrolled and start the prephase treatment with vincristine and prednisone before day 1 of cycle 1 of the experimental drugs. patients with progressive disease or stable disease after 3 cycles should start a conventional chemotherapy (r-minichop) at investigator's discretion and will remain in the study.

Eligibility criteria:
inclusion criteria: 2.patient with histologically proven cd20+ diffuse large b-cell lymphoma (dlbcl) (who classification 2017) including all clinical subtypes (primary mediastinal, intravascular, etc...), with all international prognostic index (ipi). may also be enrolled the following malignancies: * de novo transformed dlbcl from low grade lymphoma (follicular, other...) and dlbcl associated with some small cell infiltration in bone marrow or lymph node. * high-grade b-cell lymphoma with myc and bcl2 and/or bcl6 rearrangements * high-grade b-cell lymphoma, not otherwise specified (nos) * follicular lymphoma grade 3b 3.positron-emission tomography (pet)-positive disease 4.previously untreated high-grade b-cell lymphoma 5.aged ≥ 80 years old at the time of signing the informed consent form (icf) 6.ann arbor stage i, ii, iii or iv 7.eastern cooperative oncology group (eco)g performance status ≤ 2 8.with a minimum life expectancy of 3 months 9.male patients must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 4 months following study drug discontinuation, even if they have undergone a successful vasectomy 10. patients should be able to receive r-minichop regimen (left ventricular ejection fraction \> 50% and good general condition, according to investigator's judgment) 11. patients should be able to receive adequate prophylaxis and/or therapy for thromboembolic events (aspirin or low molecular weight heparin) 12. patient covered by any social security system (france) exclusion criteria: 1. any other histological type of lymphoma, burkitt included 2. any history of treated or non-treated small-b cell lymphoma prior aggressive b cell lymphoma diagnosis 3. central nervous system or meningeal involvement by lymphoma 4. any serious active disease (according to the investigator's decision) 5. poor renal function (calculated cockcroft-gault creatinine clearance \< 30 ml/min) 6. poor hepatic function (total bilirubin level \>30 μmol/l, transaminases \>2.5 upper normal limits) unless these abnormalities are related to lymphoma 7. poor bone marrow reserve as defined by neutrophils \<1.5 g/l or platelets \<100 g/l, unless related to bone marrow infiltration by lymphoma cells (bone marrow aspiration will be mandatory in case of severe cytopenias prior inclusion) 8. any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. patients previously diagnosed with prostate cancer are eligible if (1) their disease was t1-t2a, n0, m0, with a gleason score ≤7, and a prostate specific antigen (psa) ≤10 ng/ml prior to initial therapy, (2) they had definitive curative therapy (i.e., prostatectomy or radiotherapy) 2 years before day 1 of cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their psa was undetectable if they underwent prostatectomy or \<1 ng/ml if they did not undergo prostatectomy 9. treatment with any investigational drug within 30 days prior to prephase treatment and during the study 10. known hiv, active hepatitis c virus (hcv) infection or positive hepatitis b virus (hbv) test within 4 weeks before enrollment (except after hepatitis b vaccination or for patients who are hbs ag negative, anti-hbs positive and/or anti-hbc positive but viral dna negative) 11. prior treatment with anti-cd20/anti-cd19 monoclonal antibody or alemtuzumab within 3 months prior to prephase treatment 12. prior ≥ grade 3 allergic reaction/hypersensitivity to thalidomide 13. contra-indication to highly dosed glucocorticoid (60 mg/m2/d) 14. neuropathy ≥ grade 2 or painful 15. patient deprived of his/her liberty by a judicial or administrative decision 16. adult patient under legal protection