Phase III study comparing R-CODOX-M/R-IVAC versus dose-adjusted EPOCH-R (DA-EPOCH-R) for patients with newly diagnosed high risk Burkitt lymphoma

INTERVENTION: Arm A: R‐CODOX‐M/R‐IVAC 2 cycles of R‐CODOX���M and 2 cycles R‐IVAC (alternately) total of 16 weeks (4 weeks per cycle) R‐CODOX‐M consists of: ‐ rituximab i.v. (day 1,9: 375 mg/m^2/d) ‐ cyclophosphamide i.v. (day 1: 800 mg/m^2, day 2‐5: 200 mg/m^2/d) ‐ vincristine i.v. (day 1,8: 1.5 mg/d) ‐ doxorubicin i.v. (day 1: 40 mg/m^2) ‐ methotrexate i.v.(day 10: 3000 mg/m^2 (<= 65 y), 1000 mg/m^2 (> 65 y)) R‐IVAC consists of: ‐ rituximab i.v. (day 3,7: 375 mg/m^2/d) ‐ ifosfamide (day 1‐5: 1500 mg/m^2/d (<=65 y), 1000 mg/m^2/d (>65 y)) ‐ etoposide i.v. (day 1‐5: 60 mg/m^2/d) ‐ cytarabine i.v. (day 1,2: 4000 mg/^2/d (<=65 y), 2000 mg/m^2/d (>65 y) Both regimens also include supportive care and i.t. prophylaxis. Arm B: DA‐EPOCH‐R 6 cycles, 3 weeks per cycle, total of 18 weeks ‐ etoposide i.v. (day 1‐4: 50‐124.4 mg/m^2/d continuous infusion, dose adjustment possible at every cycle) ‐ prednisolone p.o. (day 1‐5 : 120 mg/m^2/d) ‐ vincristine i.v. (day 1‐4: 0.4 mg/m^2/d continuous infusion) ‐ cyclophosphamide i.v. (day 5: 480‐1866 mg/m^2/d dose adjustment possible at every cycle) ‐ doxorubicin i.v. (day 1‐4 : 10‐24.8 mg/m^2/d continuous infusion, dose adjustment possible at every cycle) ‐ rituximab i.v. (day 1,5: 375 mg/m^/d) Also with supportive care and i.t. prophylaxis. CONDITION: Non Hodkin's lymfoma (NHL), Burkitt lymphoma ; ; PRIMARY OUTCOME: 2 years EFS; time from registration to first event (death from any cause, no CR, relapse,; whichever comes first). Patients still alive or lost to follow up are censored at the date they were last known to be alive; SECONDARY OUTCOME: ‐ Overall Response Rate at end‐of‐treatment ; ; ‐ Overall Survival at 2 years; defined as time from registration until death from any cause; patients still alive or lost to follow up are censored at the date they were last known to be alive ; ; ‐ Rate of CTCAE grade >=3 toxicities ; ; ‐ Number of hospitalization days versus days in an outpatient setting ; INCLUSION CRITERIA: ‐ First diagnosis of high risk Burkitt lymphoma (sporadic and HIV associated), histologically confirmed according to the WHO classification 2008; ‐ High risk disease; i.e. any of following: elevated LDH, WHO performance status > 2, Ann Arbor stage III or IV, tumour mass > 10 cm; ‐ Age 18‐75 years inclusive; ‐ WHO performance status (PS) 0‐3, WHO PS 4 only if disease related; ‐ Written informed consent.