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

August 23, 2022 updated by: Fondazione Italiana Linfomi ONLUS

Prephase Treatment With Prednisone +/- Vitamin D Supplementation Followed by Immunochemotherapy in Elderly Patients With Diffuse Large B-Cell Lymphoma (DLBCL) A Randomized, Open Label, Phase III Study by Fondazione Italiana Linfomi.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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:

Study Type

Interventional

Enrollment (Anticipated)

430

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lorenza Randi, Dott.ssa
  • Phone Number: 0000000000
  • Email: lrandi@filinf.it

Study Contact Backup

Study Locations

  • Italy
      • Alessandria, Italy, 15121
      • Ancona, Italy, 60126
      • Ascoli Piceno, Italy, 15121
        • Not yet recruiting
        • Ascoli Piceno - Ospedale C.e G. Mazzoni - U.O.C. di Ematologia
        • Contact:
        • Principal Investigator:
          • Pietro Galieni, MD
      • Aviano, Italy
        • Recruiting
        • Aviano - Centro Riferimento Oncologico - S.O.C. Oncologia Medica A
        • Contact:
      • Barletta, Italy
        • Not yet recruiting
        • Barletta - Ospedale "Monsignor Raffaele Dimiccoli" - Ematologia
        • Contact:
      • Bergamo, Italy
        • Not yet recruiting
        • Bergamo - Cliniche Humanitas Gavazzeni - Oncologia - Cliniche Humanitas Gavazzeni
        • Principal Investigator:
          • Serena Camilla Dalto, MD
        • Contact:
      • Biella, Italy
        • Not yet recruiting
        • Biella - Ospedale Degli Infermi - S.C. Oncologia
        • Contact:
        • Principal Investigator:
          • Annarita Conconi, MD
      • Campobasso, Italy
        • Not yet recruiting
        • Campobasso - Universitа Cattolica del Sacro Cuore - Ematologia
        • Contact:
        • Principal Investigator:
          • Sergio Storti, MD
      • Castelfranco Veneto, Italy
        • Not yet recruiting
        • Castelfranco Veneto - Ospedale di Castelfranco Veneto - Ematologia
        • Contact:
        • Principal Investigator:
          • Roberto Sartori, MD
      • Firenze, Italy
        • Recruiting
        • Unità Funzionale di Ematologia AOU Careggi
        • Contact:
        • Principal Investigator:
          • Benedetta Puccini, MD
      • Frosinone, Italy
        • Not yet recruiting
        • Frosinone - Presidio Ospedaliero F. Spaziani - UOC Ematologia
        • Contact:
        • Principal Investigator:
          • Gabriella Tomei, MD
      • Matera, Italy
        • Not yet recruiting
        • Matera - Ospedale Madonna delle Grazie - Ematologia
        • Contact:
        • Principal Investigator:
          • Clara Mannarella, MD
      • Meldola, Italy
        • Recruiting
        • Meldola - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
        • Contact:
        • Principal Investigator:
          • Fabio Augello, MD
      • Mestre, Italy
        • Not yet recruiting
        • Mestre - Ospedale Dell Angelo - U.O. Ematologia
        • Contact:
        • Principal Investigator:
          • Renato Bassan, MD
      • Milano, Italy, 20162
      • Monza, Italy
        • Recruiting
        • Monza - ASST MONZA Ospedale S. Gerardo - Ematologia
        • Contact:
        • Principal Investigator:
          • Ivana Casaroli, MD
      • Napoli, Italy
        • Not yet recruiting
        • Napoli - AOU Universitа degli Studi della Campania Luigi Vanvitelli - Oncologia Medica ed Ematologia
        • Contact:
        • Principal Investigator:
          • Antonello Sica, MD
      • Novara, Italy, 28100
      • Padova, Italy
        • Not yet recruiting
        • Padova - I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
        • Contact:
      • Pagani, Italy
        • Not yet recruiting
        • Pagani - Presidio ospedaliero "A. TORTORA" - U.O. Onco-ematologia
        • Contact:
        • Principal Investigator:
          • Catello Califano, MD
      • Palermo, Italy
        • Not yet recruiting
        • Palermo - A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
        • Contact:
      • Palermo, Italy
      • Pavia, Italy
        • Recruiting
        • UO Ematologia Università - Policlinico San Matteo
        • Contact:
        • Principal Investigator:
          • Luca Arcaini, MD
      • Pescara, Italy
        • Not yet recruiting
        • Pescara - P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi
        • Contact:
        • Principal Investigator:
          • Elsa Pennese, MD
        • Contact:
      • Potenza, Italy
        • Not yet recruiting
        • Potenza - AOR San Carlo
        • Contact:
        • Principal Investigator:
          • Michele Ciminiello, MD
      • Ravenna, Italy
        • Recruiting
        • UO Ematologia Ospedale Santa Maria delle Croci
        • Contact:
        • Principal Investigator:
          • Monica Tani, MD
      • Reggio Emilia, Italy, 42123
      • Rimini, Italy
        • Not yet recruiting
        • UO Ematologia - Ospedale degli Infermi
        • Contact:
        • Principal Investigator:
          • Anna Lia Molinari, MD
      • Roma, Italy
        • Not yet recruiting
        • Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive
        • Contact:
        • Principal Investigator:
          • Michele Bibas, MD
      • Roma, Italy
        • Not yet recruiting
        • Roma - Ospedale S. Camillo - Ematologia
        • Contact:
        • Principal Investigator:
          • Luigi Rigacci, MD
      • Roma, Italy
        • Recruiting
        • Roma - Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare
        • Principal Investigator:
          • Ombretta Annibali, MD
        • Contact:
      • Roma, Italy
        • Not yet recruiting
        • Università Cattolica S. Cuore, Ematologia
        • Contact:
      • Roma, Italy
        • Not yet recruiting
        • Università La Sapienza Ematologia
        • Contact:
        • Principal Investigator:
          • Alice Di Rocco, MD
      • Roma, Italy
        • Not yet recruiting
        • UOC Ematologia - A.O. Sant'Andrea
        • Contact:
        • Principal Investigator:
          • Agostino Tafuri, MD
      • Salerno, Italy
        • Recruiting
        • Salerno - Ematologia e Trapianti A.O. San Giovanni di Dio e Ruggi D Aragona - U.O. Ematologia
        • Contact:
      • San Giovanni Rotondo, Italy
        • Not yet recruiting
        • San Giovanni Rotondo - Casa Sollievo della Sofferenza - U.O. Ematologia
        • Contact:
      • Sassari, Italy
        • Not yet recruiting
        • Sassari - AOU di Sassari - Ematologia
        • Contact:
        • Principal Investigator:
          • Claudio Fozza, MD
      • Sassuolo, Italy
        • Recruiting
        • UOC Medicina Interna MO DH Oncologico
        • Contact:
        • Principal Investigator:
          • Sara Bigliardi, MD
      • Siena, Italy
      • Terni, Italy
        • Recruiting
        • Univ. Perugia Sede Terni - Oncoematologia
        • Contact:
        • Principal Investigator:
          • Anna Marina Liberati, MD
      • Torino, Italy, 10126
        • Recruiting
        • AOU Citta della Salute e della Scienza di Torino - Ematologia Universitaria
        • Principal Investigator:
          • Federica Cavallo, MD
        • Contact:
        • Contact:
          • Luca Palumbo
      • Torino, Italy
        • Recruiting
        • SC. Ematologia A.O. Città della Salute e della Scienza
        • Principal Investigator:
          • Barbara Botto, MD
        • Contact:
        • Contact:
          • Giorgio Priolo
      • Torino, Italy
        • Not yet recruiting
        • Torino - San Giovanni Bosco - ASL Cittа di Torino - SSD di Ematologia e Malattie Trombotiche
        • Contact:
        • Principal Investigator:
          • Federica De marco, MD
      • Trieste, Italy, 34121
      • Udine, Italy
      • Vicenza, Italy
        • Recruiting
        • ULSS 8 Berica - Ospedale S. Bortolo - Ematologia
        • Contact:
        • Principal Investigator:
          • Maria Chiara Tisi, MD
    • BS
    • PC
      • Piacenza, PC, Italy, 29121
        • Recruiting
        • UO Ematologia e CTMO di Piacenza
        • Contact:
    • Piacenza
      • Rionero in Vulture, Piacenza, Italy
        • Not yet recruiting
        • Ospedale Oncologico regionale CROB
        • Contact:
        • Principal Investigator:
          • Giuseppe Pietrantuono, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

61 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  1. 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.
  2. Age ≥ 65 years
  3. Comprehensive Geriatric Assessment performed at baseline, before start of any treatment.
  4. Eastern Cooperative Oncology Group performance status (PS) ≤3
  5. Eligibility for anthracycline containing regimen (R-CHOP or R-miniCHOP)
  6. No previous treatment for DLBCL or Follicular grade IIIb lymphoma
  7. Ann Arbor stage I-IV
  8. 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
  9. Serum basic levels of Vitamin D [25 (OH) VitD] ≤ 40 ng / ml;

  10. 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

  11. Adequate renal function defined as follows:

    - Creatinine ≤ 2 mg/dL, unless secondary to lymphoma

  12. Adequate hepatic function defined as follows:

    - Bilirubin ≤ 2 mg/dL unless secondary to lymphoma

  13. LVEF > 50% at bidimensionally echocardiogram
  14. Life expectancy ≥ 6 months
  15. Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee , prior to the initiation of any screening or study-specific procedures
  16. Subject must be able to adhere to the study visit schedule and other protocol requirements
  17. Men must agree to use one of the below reported acceptable method of contraception for the duration of the study and for 3 months after receiving the last dose of immunochemotherapy, and to not donate sperm while on study.

Exclusion criteria

  1. 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)
  2. Use of VitD supplementation as standard of care at dose higher than 10,000 U/week
  3. Suspect or clinical evidence of CNS involvement by lymphoma
  4. Contraindication to the use of rituximab
  5. Contraindication to the use of VitD supplementation (Hypercalcemia/Hyperphosphatemia)
  6. 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
  7. 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
  8. 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

  9. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm B (Experimental):

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.
Drug: Vitamin D3 (Cholecalciferol)
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.
Drug: RCHOP o R-miniCHOP at standard doses

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
Other: Arm A (Standard arm)

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
Drug: RCHOP o R-miniCHOP at standard doses

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: at the end of treatment - 54 months
Progression-Free Survival
at the end of treatment - 54 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: at the end of treatment - 54 months
Overall Survival
at the end of treatment - 54 months
Event Free Survival
Time Frame: at the end of treatment - 54 months
Event Free Survival (EFS)
at the end of treatment - 54 months
Response rate
Time Frame: at the end of treatment - 54 months
Response rate
at the end of treatment - 54 months
Early death rate
Time Frame: at the end of treatment - 54 months
Early death rate
at the end of treatment - 54 months
Rate of ECOG changes after prephase
Time Frame: at the end of treatment - 54 months
Rate of ECOG changes after prephase
at the end of treatment - 54 months
Rate of patients who maintain 25(OH)VitD levels
Time Frame: At the beginning of Cycle 2 (each cycle is 21 days)
Rate of patients who maintain 25(OH)VitD levels
At the beginning of Cycle 2 (each cycle is 21 days)
Rate of 25(OH)VitD correction (VitD supplementation arm)
Time Frame: At the beginning of Cycle 2 (each cycle is 21 days)
Rate of 25(OH)VitD correction (VitD supplementation arm)
At the beginning of Cycle 2 (each cycle is 21 days)
time-to-deterioration physical functioning and fatigue
Time Frame: At the beginning of Cycle 2 (each cycle is 21 days)
time-to-deterioration physical functioning and fatigue
At the beginning of Cycle 2 (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Italiana Linfomi ONLUS

Collaborators

GRADE Onlus

Investigators

  • Principal Investigator: Francesco Merli, Dott., Reggio Emilia - Azienda Unitа Sanitaria Locale-IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2021

Primary Completion (Anticipated)

September 1, 2025

Study Completion (Anticipated)

September 1, 2030

Study Registration Dates

First Submitted

May 26, 2020

First Submitted That Met QC Criteria

June 19, 2020

First Posted (Actual)

June 22, 2020

Study Record Updates

Last Update Posted (Actual)

August 26, 2022

Last Update Submitted That Met QC Criteria

August 23, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIL_PREVID

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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