Prephase Treatment With Prednisone +/- Vitamin D Supplementation Followed by Immunochemotherapy
FIL_PREVID
1 other identifier
interventional
430
1 country
49
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2021
Longer than P75 for phase_3
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 26, 2020
CompletedFirst Posted
Study publicly available on registry
June 22, 2020
CompletedStudy Start
First participant enrolled
March 23, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2030
ExpectedAugust 26, 2022
August 1, 2022
4.4 years
May 26, 2020
August 23, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival
Progression-Free Survival
at the end of treatment - 54 months
Secondary Outcomes (8)
Overall Survival
at the end of treatment - 54 months
Event Free Survival
at the end of treatment - 54 months
Response rate
at the end of treatment - 54 months
Early death rate
at the end of treatment - 54 months
Rate of ECOG changes after prephase
at the end of treatment - 54 months
- +3 more secondary outcomes
Study Arms (2)
Arm B (Experimental):
EXPERIMENTALPatients 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)
OTHERPatients 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
Interventions
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 (CGA) result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.
Patients on both arms receive pre-treatment with prednisone oral before 6 cycles of 21 days each of immunochemotherapy with RCHOP o R-miniCHOP at standard doses
Eligibility Criteria
You may qualify if:
- Histologically documented diagnosis of Diffuse Large B-cell Lymphoma or Follicular grade IIIb lymphoma, as defined in the 2017 edition of the World Health Organization (WHO) classification.
- Age ≥ 65 years
- Comprehensive Geriatric Assessment performed at baseline, before start of any treatment.
- Eastern Cooperative Oncology Group performance status (PS) ≤3
- Eligibility for anthracycline containing regimen (R-CHOP or R-miniCHOP)
- No previous treatment for DLBCL or Follicular grade IIIb lymphoma
- Ann Arbor stage I-IV
- At least one site of measurable nodal disease at baseline ≥ 1.5 cm in the longest transverse diameter as determined by CT scan ; or one metabolic active site of disease at baseline FDG-PET scan
- Serum basic levels of Vitamin D \[25 (OH) VitD\] ≤ 40 ng / ml;
- Adequate hematological counts defined as follows:
- Absolute Neutrophil count \> 1.5 x 109/L unless due to bone marrow involvement by lymphoma
- Platelet count ≥ 80.000/mm3 unless due to bone marrow involvement by lymphoma
- Adequate renal function defined as follows:
- \- Creatinine ≤ 2 mg/dL, unless secondary to lymphoma
- Adequate hepatic function defined as follows:
- +6 more criteria
You may not qualify if:
- Histological diagnosis different from Diffuse large B-Cell Lymphoma or Follicular grade IIIb lymphoma, including diagnosis of HGBL, with rearrangement of MYC, BCL2 and/or BCL6 (double-hit)
- Use of VitD supplementation as standard of care at dose higher than 10,000 U/week
- Suspect or clinical evidence of CNS involvement by lymphoma
- Contraindication to the use of rituximab
- Contraindication to the use of VitD supplementation (Hypercalcemia/Hyperphosphatemia)
- Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug
- Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent
- Any history of other active malignancies within 2 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin or limited stage surgically removed breast cancer or adequately treated with radiation therapy or limited stage prostate carcinoma surgically removed or adequately treated with radiation therapy or previous malignancy confined and surgically resected with curative intent
- Evidence of other clinically significant uncontrolled condition including, but not limited to:
- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- Chronic hepatitis B virus or hepatitis C requiring treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fondazione Italiana Linfomi - ETSlead
- GRADE Onluscollaborator
Study Sites (49)
SC Ematologia Spedali Civili
Brescia, BS, Italy
UO Ematologia e CTMO di Piacenza
Piacenza, PC, 29121, Italy
Ospedale Oncologico regionale CROB
Rionero in Vulture, Piacenza, Italy
A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C. Ematologia
Alessandria, 15121, Italy
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
Ancona, 60126, Italy
Ascoli Piceno - Ospedale C.e G. Mazzoni - U.O.C. di Ematologia
Ascoli Piceno, 15121, Italy
Aviano - Centro Riferimento Oncologico - S.O.C. Oncologia Medica A
Aviano, Italy
Barletta - Ospedale "Monsignor Raffaele Dimiccoli" - Ematologia
Barletta, Italy
Bergamo - Cliniche Humanitas Gavazzeni - Oncologia - Cliniche Humanitas Gavazzeni
Bergamo, Italy
Biella - Ospedale Degli Infermi - S.C. Oncologia
Biella, Italy
Campobasso - Universitа Cattolica del Sacro Cuore - Ematologia
Campobasso, Italy
Castelfranco Veneto - Ospedale di Castelfranco Veneto - Ematologia
Castelfranco Veneto, Italy
Unità Funzionale di Ematologia AOU Careggi
Florence, Italy
Frosinone - Presidio Ospedaliero F. Spaziani - UOC Ematologia
Frosinone, Italy
Matera - Ospedale Madonna delle Grazie - Ematologia
Matera, Italy
Meldola - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
Meldola, Italy
Mestre - Ospedale Dell Angelo - U.O. Ematologia
Mestre, Italy
SC Ematologia AO Niguarda Cà Granda
Milan, 20162, Italy
Monza - ASST MONZA Ospedale S. Gerardo - Ematologia
Monza, Italy
Napoli - AOU Universitа degli Studi della Campania Luigi Vanvitelli - Oncologia Medica ed Ematologia
Napoli, Italy
Università del Piemonte Orientale - Novara
Novara, 28100, Italy
Padova - I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
Padua, Italy
Pagani - Presidio ospedaliero "A. TORTORA" - U.O. Onco-ematologia
Pagani, Italy
Palermo - A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
Palermo, Italy
Palermo - AOU Policlinico Giaccone - Ematologia
Palermo, Italy
UO Ematologia Università - Policlinico San Matteo
Pavia, Italy
Pescara - P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi
Pescara, Italy
Potenza - AOR San Carlo
Potenza, Italy
UO Ematologia Ospedale Santa Maria delle Croci
Ravenna, Italy
Reggio Emilia - AO Santa Maria Nuova
Reggio Emilia, 42123, Italy
UO Ematologia - Ospedale degli Infermi
Rimini, Italy
Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive
Roma, Italy
Roma - Ospedale S. Camillo - Ematologia
Roma, Italy
Roma - Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare
Roma, Italy
Università Cattolica S. Cuore, Ematologia
Roma, Italy
Università La Sapienza Ematologia
Roma, Italy
UOC Ematologia - A.O. Sant'Andrea
Roma, Italy
Salerno - Ematologia e Trapianti A.O. San Giovanni di Dio e Ruggi D Aragona - U.O. Ematologia
Salerno, Italy
San Giovanni Rotondo - Casa Sollievo della Sofferenza - U.O. Ematologia
San Giovanni Rotondo, Italy
Sassari - AOU di Sassari - Ematologia
Sassari, Italy
UOC Medicina Interna MO DH Oncologico
Sassuolo, Italy
UOC Ematologia, AOU Senese
Siena, Italy
Univ. Perugia Sede Terni - Oncoematologia
Terni, Italy
AOU Citta della Salute e della Scienza di Torino - Ematologia Universitaria
Torino, 10126, Italy
SC. Ematologia A.O. Città della Salute e della Scienza
Torino, Italy
Torino - San Giovanni Bosco - ASL Cittа di Torino - SSD di Ematologia e Malattie Trombotiche
Torino, Italy
Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia
Trieste, 34121, Italy
Udine - Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica
Udine, Italy
ULSS 8 Berica - Ospedale S. Bortolo - Ematologia
Vicenza, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Francesco Merli, Dott.
Reggio Emilia - Azienda Unitа Sanitaria Locale-IRCCS
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 26, 2020
First Posted
June 22, 2020
Study Start
March 23, 2021
Primary Completion
September 1, 2025
Study Completion (Estimated)
September 1, 2030
Last Updated
August 26, 2022
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will not share
This is an open-label, multicenter, randomized phase III trial. The study plans to randomize patients with a 1:1 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 (CGA) result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.