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

NCT ID: NCT04442412

Last Updated: 2022-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

430 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-23

Study Completion Date

2030-09-01

Brief Summary

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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

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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:

Conditions

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Diffuse Large B-Cell Lymphoma Elderly Patients

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Vitamin D3 (Cholecalciferol)

Intervention Type DRUG

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.

RCHOP o R-miniCHOP at standard doses

Intervention Type DRUG

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

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

Group Type OTHER

RCHOP o R-miniCHOP at standard doses

Intervention Type DRUG

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

Interventions

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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.

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GRADE Onlus

OTHER

Sponsor Role collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Francesco Merli, Dott.

Role: PRINCIPAL_INVESTIGATOR

Reggio Emilia - Azienda Unitа Sanitaria Locale-IRCCS

Locations

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SC Ematologia Spedali Civili

Brescia, BS, Italy

Site Status RECRUITING

UO Ematologia e CTMO di Piacenza

Piacenza, PC, Italy

Site Status RECRUITING

Ospedale Oncologico regionale CROB

Rionero in Vulture, Piacenza, Italy

Site Status NOT_YET_RECRUITING

A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C. Ematologia

Alessandria, , Italy

Site Status RECRUITING

A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona

Ancona, , Italy

Site Status RECRUITING

Ascoli Piceno - Ospedale C.e G. Mazzoni - U.O.C. di Ematologia

Ascoli Piceno, , Italy

Site Status NOT_YET_RECRUITING

Aviano - Centro Riferimento Oncologico - S.O.C. Oncologia Medica A

Aviano, , Italy

Site Status RECRUITING

Barletta - Ospedale "Monsignor Raffaele Dimiccoli" - Ematologia

Barletta, , Italy

Site Status NOT_YET_RECRUITING

Bergamo - Cliniche Humanitas Gavazzeni - Oncologia - Cliniche Humanitas Gavazzeni

Bergamo, , Italy

Site Status NOT_YET_RECRUITING

Biella - Ospedale Degli Infermi - S.C. Oncologia

Biella, , Italy

Site Status NOT_YET_RECRUITING

Campobasso - Universitа Cattolica del Sacro Cuore - Ematologia

Campobasso, , Italy

Site Status NOT_YET_RECRUITING

Castelfranco Veneto - Ospedale di Castelfranco Veneto - Ematologia

Castelfranco Veneto, , Italy

Site Status NOT_YET_RECRUITING

Unità Funzionale di Ematologia AOU Careggi

Florence, , Italy

Site Status RECRUITING

Frosinone - Presidio Ospedaliero F. Spaziani - UOC Ematologia

Frosinone, , Italy

Site Status NOT_YET_RECRUITING

Matera - Ospedale Madonna delle Grazie - Ematologia

Matera, , Italy

Site Status NOT_YET_RECRUITING

Meldola - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia

Meldola, , Italy

Site Status RECRUITING

Mestre - Ospedale Dell Angelo - U.O. Ematologia

Mestre, , Italy

Site Status NOT_YET_RECRUITING

SC Ematologia AO Niguarda Cà Granda

Milan, , Italy

Site Status NOT_YET_RECRUITING

Monza - ASST MONZA Ospedale S. Gerardo - Ematologia

Monza, , Italy

Site Status RECRUITING

Napoli - AOU Universitа degli Studi della Campania Luigi Vanvitelli - Oncologia Medica ed Ematologia

Napoli, , Italy

Site Status NOT_YET_RECRUITING

Università del Piemonte Orientale - Novara

Novara, , Italy

Site Status NOT_YET_RECRUITING

Padova - I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1

Padua, , Italy

Site Status NOT_YET_RECRUITING

Pagani - Presidio ospedaliero "A. TORTORA" - U.O. Onco-ematologia

Pagani, , Italy

Site Status NOT_YET_RECRUITING

Palermo - A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia

Palermo, , Italy

Site Status NOT_YET_RECRUITING

Palermo - AOU Policlinico Giaccone - Ematologia

Palermo, , Italy

Site Status RECRUITING

UO Ematologia Università - Policlinico San Matteo

Pavia, , Italy

Site Status RECRUITING

Pescara - P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi

Pescara, , Italy

Site Status NOT_YET_RECRUITING

Potenza - AOR San Carlo

Potenza, , Italy

Site Status NOT_YET_RECRUITING

UO Ematologia Ospedale Santa Maria delle Croci

Ravenna, , Italy

Site Status RECRUITING

Reggio Emilia - AO Santa Maria Nuova

Reggio Emilia, , Italy

Site Status RECRUITING

UO Ematologia - Ospedale degli Infermi

Rimini, , Italy

Site Status NOT_YET_RECRUITING

Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive

Roma, , Italy

Site Status NOT_YET_RECRUITING

Roma - Ospedale S. Camillo - Ematologia

Roma, , Italy

Site Status NOT_YET_RECRUITING

Roma - Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare

Roma, , Italy

Site Status RECRUITING

Università Cattolica S. Cuore, Ematologia

Roma, , Italy

Site Status NOT_YET_RECRUITING

Università La Sapienza Ematologia

Roma, , Italy

Site Status NOT_YET_RECRUITING

UOC Ematologia - A.O. Sant'Andrea

Roma, , Italy

Site Status NOT_YET_RECRUITING

Salerno - Ematologia e Trapianti A.O. San Giovanni di Dio e Ruggi D Aragona - U.O. Ematologia

Salerno, , Italy

Site Status RECRUITING

San Giovanni Rotondo - Casa Sollievo della Sofferenza - U.O. Ematologia

San Giovanni Rotondo, , Italy

Site Status NOT_YET_RECRUITING

Sassari - AOU di Sassari - Ematologia

Sassari, , Italy

Site Status NOT_YET_RECRUITING

UOC Medicina Interna MO DH Oncologico

Sassuolo, , Italy

Site Status RECRUITING

UOC Ematologia, AOU Senese

Siena, , Italy

Site Status RECRUITING

Univ. Perugia Sede Terni - Oncoematologia

Terni, , Italy

Site Status RECRUITING

AOU Citta della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, , Italy

Site Status RECRUITING

SC. Ematologia A.O. Città della Salute e della Scienza

Torino, , Italy

Site Status RECRUITING

Torino - San Giovanni Bosco - ASL Cittа di Torino - SSD di Ematologia e Malattie Trombotiche

Torino, , Italy

Site Status NOT_YET_RECRUITING

Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

Trieste, , Italy

Site Status RECRUITING

Udine - Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica

Udine, , Italy

Site Status NOT_YET_RECRUITING

ULSS 8 Berica - Ospedale S. Bortolo - Ematologia

Vicenza, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Lorenza Randi, Dott.ssa

Role: CONTACT

0000000000

Francesco Merli, Dott.

Role: CONTACT

0000000000

Facility Contacts

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Alessandra Tucci

Role: primary

Annalisa Arcari, MD

Role: primary

Giuseppe Pietrantuono, MD

Role: primary

Manuela Zanni, MD

Role: primary

Maria Vittoria Sacchi

Role: backup

Guido Gini

Role: primary

Alessandra Barucca

Role: backup

Piero Galieni, MD

Role: primary

Michele Spina, MD

Role: primary

Giuseppe Tarantini, MD

Role: primary

Serena Camilla Dalto

Role: primary

Annarita Conconi, MD

Role: primary

Sergio Storti, MD

Role: primary

Roberto Sartori, MD

Role: primary

Benedetta Puccini, MD

Role: primary

Gabriella Tomei, MD

Role: primary

Clara Mannarella, MD

Role: primary

Fabio Augello, MD

Role: primary

Renato Bassan, MD

Role: primary

Emanuele Ravano, MD

Role: primary

Isabella Ghislandi

Role: backup

Ivana Casaroli, MD

Role: primary

Antonello Sica, MD

Role: primary

Gianluca Gaidano, MD

Role: primary

0321/660655

Clara Deambrogi

Role: backup

Dario Marino, MD

Role: primary

Catello Califano, MD

Role: primary

Caterina Patti, MD

Role: primary

Salvatrice Mancuso, MD

Role: primary

Luca Arcaini, MD

Role: primary

Elsa Pennese, MD

Role: primary

Stefania Luciani

Role: backup

Michele Cimminiello, MD

Role: primary

Monica Tani, MD

Role: primary

Francesco Merli, MD

Role: primary

0522-296618

Caterina Mammi

Role: backup

Anna Lia Molinari, MD

Role: primary

Michele Bibas, MD

Role: primary

Luigi Rigacci, MD

Role: primary

Ombretta Annibali, MD

Role: primary

Stefan Hohaus, MD

Role: primary

Alice Di Rocco, MD

Role: primary

Agostino Tafuri, MD

Role: primary

0633775113

Carmine Selleri, MD

Role: primary

Nicola Cascavilla, MD

Role: primary

Claudio Fozza, MD

Role: primary

Sara Bigliardi, MD

Role: primary

Alberto Fabbri, MD

Role: primary

Cristiana Cafarelli

Role: backup

Anna Marina Liberati, MD

Role: primary

Federica Cavallo, MD

Role: primary

+39 0116334264

Luca Palumbo

Role: backup

Barbara Botto, MD

Role: primary

Giorgio Priolo

Role: backup

Federica De marco, MD

Role: primary

Francesco Zaja, MD

Role: primary

Marta De Piccoli

Role: backup

Jacopo Olivieri, MD

Role: primary

Cristina D'Odorico

Role: backup

Maria Chiara Tisi, MD

Role: primary

Other Identifiers

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FIL_PREVID

Identifier Type: -

Identifier Source: org_study_id

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