Prephase Treatment With Prednisone +/- Vitamin D Supplementation Followed by Immunochemotherapy

After the patient signs the written informed consent the patient will enter the screening phase planning baseline assessments and will be randomly allocated with a 1 to 1 ratio to Arm A (Standard arm) or Arm B (Experimental arm). Patients randomized to Arm A will receive a prephase with oral prednisone (50 mg for 7 days \[day -6 to day 0\]) followed by 6 courses of R-CHOP or R-miniCHOP every 21 days. If patients randomized to arm A are already on VitD, they are allowed to continue receiving VitD supplementation at a dose that can be considered part of the standard of care and does not exceed the maximum standard VitD dose recommended for general adult and elderly population , up to 10,000 U/week VitD . If clinically indicated at treating physician judgement, patients could receive 1 mg of vincristine on the first day of prephase ; in this case vincristine administration in cycle 1 of immunochemotherapy should be skipped, in patients receiving R-miniCHOP; reduced to 1 mg, in patients receiving R-CHOP. Patients randomized to Arm B will receive a prephase with oral prednisone and a prephase therapy with VitD according to the below reported schedule followed by 6 courses of R-CHOP or R-miniCHOP every 21 days. Schedule for VitD (Cholecalciferol) supplementation: 25,000 U/day starting on day -6: daily loading dose for 7 days if 25 VitD baseline level 20-40 ng/ml daily loading dose for 14 days if 25 VitD baseline level \< 20 ng/ml followed by weekly maintenance supplementation of 25,000 U for the entire duration of immunochemotherapy (6 courses every 21 days - 18 weeks), regardless of the baseline level of 25 VitD. If clinically indicated at treating physician judgement, patients could receive 1 mg of vincristine on the first day of prephase (DAY -6); in this case vincristine administration in cycle 1 of immunochemotherapy should be: skipped, in patients receiving R-miniCHOP; reduced to 1 mg, in patients receiving R-CHOP. Patients with 25(OH)VitD levels \<30 ng/ml on d1 cycle 2 will receive and additional loading phase of Cholecalciferol 25,000 U/day for 7 days and then 25,000 U once weekly for the duration of immunochemotherapy. Patients may continue with VitD supplementation after the end of the immunochemotherapy at a (reduced) standard dose of 25,000 U once a month for up to 2 years from end of immunochemotherapy. Patients experimenting toxicity leading to a delay in treatment administration \> 4 weeks will discontinue study treatment and will be addressed to a salvage treatment: these patients will be followed-up for survival until the end of the study. Consolidation radiotherapy: