Prephase Treatment With Prednisone +/- Vitamin D Supplementation Followed by Immunochemotherapy
- Conditions
- Diffuse Large B-Cell LymphomaElderly Patients
- Interventions
- Drug: Vitamin D3 (Cholecalciferol)Drug: RCHOP o R-miniCHOP at standard doses
- Registration Number
- NCT04442412
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- Brief Summary
This is an open-label, multicenter, randomized phase III trial. The study plans to randomize patients with a 1 to 1 ratio to Arm A (Standard arm) or Arm B (Experimental arm).
All patients of both arms will receive a prephase with oral prednisone before 6 cycles Q21 of immunochemotherapy with R-CHOP or R-miniCHOP at standard doses; patients in the Experimental arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD during the intere period of immunochemotherapy according to a prefixed schedule. Choice of type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.
- Detailed Description
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:
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 430
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (Experimental): Vitamin D3 (Cholecalciferol) 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 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. Arm B (Experimental): RCHOP o R-miniCHOP at standard doses 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 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. Arm A (Standard arm) RCHOP o R-miniCHOP at standard doses Patients randomized to Arm A will receive a prephase with oral prednisone 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
- Primary Outcome Measures
Name Time Method Progression-Free Survival at the end of treatment - 54 months Progression-Free Survival
- Secondary Outcome Measures
Name Time Method Event Free Survival at the end of treatment - 54 months Event Free Survival (EFS)
Early death rate at the end of treatment - 54 months Early death rate
Rate of ECOG changes after prephase at the end of treatment - 54 months Rate of ECOG changes after prephase
Rate of patients who maintain 25(OH)VitD levels At the beginning of Cycle 2 (each cycle is 21 days) Rate of patients who maintain 25(OH)VitD levels
Rate of 25(OH)VitD correction (VitD supplementation arm) At the beginning of Cycle 2 (each cycle is 21 days) Rate of 25(OH)VitD correction (VitD supplementation arm)
time-to-deterioration physical functioning and fatigue At the beginning of Cycle 2 (each cycle is 21 days) time-to-deterioration physical functioning and fatigue
Overall Survival at the end of treatment - 54 months Overall Survival
Response rate at the end of treatment - 54 months Response rate
Trial Locations
- Locations (49)
Matera - Ospedale Madonna delle Grazie - Ematologia
š®š¹Matera, Italy
Ascoli Piceno - Ospedale C.e G. Mazzoni - U.O.C. di Ematologia
š®š¹Ascoli Piceno, Italy
Ospedale Oncologico regionale CROB
š®š¹Rionero in Vulture, Piacenza, Italy
SC Ematologia Spedali Civili
š®š¹Brescia, BS, Italy
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
š®š¹Ancona, Italy
Barletta - Ospedale "Monsignor Raffaele Dimiccoli" - Ematologia
š®š¹Barletta, Italy
Aviano - Centro Riferimento Oncologico - S.O.C. Oncologia Medica A
š®š¹Aviano, Italy
Castelfranco Veneto - Ospedale di Castelfranco Veneto - Ematologia
š®š¹Castelfranco Veneto, Italy
SC Ematologia AO Niguarda CĆ Granda
š®š¹Milano, Italy
Monza - ASST MONZA Ospedale S. Gerardo - Ematologia
š®š¹Monza, Italy
Palermo - A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
š®š¹Palermo, Italy
UniversitĆ del Piemonte Orientale - Novara
š®š¹Novara, Italy
Palermo - AOU Policlinico Giaccone - Ematologia
š®š¹Palermo, Italy
UO Ematologia Ospedale Santa Maria delle Croci
š®š¹Ravenna, Italy
Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive
š®š¹Roma, Italy
Reggio Emilia - AO Santa Maria Nuova
š®š¹Reggio Emilia, Italy
UO Ematologia - Ospedale degli Infermi
š®š¹Rimini, Italy
Roma - Ospedale S. Camillo - Ematologia
š®š¹Roma, Italy
Roma - Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare
š®š¹Roma, Italy
UniversitĆ Cattolica S. Cuore, Ematologia
š®š¹Roma, Italy
UniversitĆ La Sapienza Ematologia
š®š¹Roma, Italy
UOC Ematologia - A.O. Sant'Andrea
š®š¹Roma, Italy
San Giovanni Rotondo - Casa Sollievo della Sofferenza - U.O. Ematologia
š®š¹San Giovanni Rotondo, Italy
Torino - San Giovanni Bosco - ASL CittŠ° di Torino - SSD di Ematologia e Malattie Trombotiche
š®š¹Torino, Italy
AOU Citta della Salute e della Scienza di Torino - Ematologia Universitaria
š®š¹Torino, Italy
Udine - Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica
š®š¹Udine, Italy
ULSS 8 Berica - Ospedale S. Bortolo - Ematologia
š®š¹Vicenza, Italy
UO Ematologia e CTMO di Piacenza
š®š¹Piacenza, PC, Italy
A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C. Ematologia
š®š¹Alessandria, Italy
Biella - Ospedale Degli Infermi - S.C. Oncologia
š®š¹Biella, Italy
Campobasso - UniversitŠ° Cattolica del Sacro Cuore - Ematologia
š®š¹Campobasso, Italy
Bergamo - Cliniche Humanitas Gavazzeni - Oncologia - Cliniche Humanitas Gavazzeni
š®š¹Bergamo, Italy
Meldola - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
š®š¹Meldola, Italy
Mestre - Ospedale Dell Angelo - U.O. Ematologia
š®š¹Mestre, Italy
UnitĆ Funzionale di Ematologia AOU Careggi
š®š¹Firenze, Italy
Frosinone - Presidio Ospedaliero F. Spaziani - UOC Ematologia
š®š¹Frosinone, Italy
Napoli - AOU UniversitŠ° degli Studi della Campania Luigi Vanvitelli - Oncologia Medica ed Ematologia
š®š¹Napoli, Italy
Padova - I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
š®š¹Padova, Italy
UO Ematologia UniversitĆ - Policlinico San Matteo
š®š¹Pavia, Italy
Pagani - Presidio ospedaliero "A. TORTORA" - U.O. Onco-ematologia
š®š¹Pagani, Italy
Pescara - P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi
š®š¹Pescara, Italy
Potenza - AOR San Carlo
š®š¹Potenza, Italy
Salerno - Ematologia e Trapianti A.O. San Giovanni di Dio e Ruggi D Aragona - U.O. Ematologia
š®š¹Salerno, Italy
Sassari - AOU di Sassari - Ematologia
š®š¹Sassari, Italy
UOC Medicina Interna MO DH Oncologico
š®š¹Sassuolo, Italy
Univ. Perugia Sede Terni - Oncoematologia
š®š¹Terni, Italy
UOC Ematologia, AOU Senese
š®š¹Siena, Italy
SC. Ematologia A.O. CittĆ della Salute e della Scienza
š®š¹Torino, Italy
Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia
š®š¹Trieste, Italy