Clinical trial • Phase III • Oncology | Haematology

Colecalciferol for Diffuse large B-cell lymphoma | Follicular lymphoma grade IIIb

Phase III trial of Colecalciferol for Diffuse large B-cell lymphoma | Follicular lymphoma grade IIIb.

Overview

Trial Therapeutic Area
Oncology | Haematology
Trial Disease
Diffuse large B-cell lymphoma | Follicular lymphoma grade IIIb
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
25-10-2024
First CTIS Authorization Date
18-11-2024

Trial design

Randomised, open-label, prephase: oral prednisone alone versus oral prednisone plus vitamin d (colecalciferol) supplementation; both arms followed by 6 cycles of conventional immunochemotherapy (r-chop or r-minichop). prednisone product details in part i: prednisone (product listing) with max daily dose 50 mg; colecalciferol listed as oral vitamin d (product listing).-controlled Phase III trial across 45 sites in Italy.

Randomised
Yes
Open Label
Yes
Comparator
Prephase: oral prednisone alone versus oral prednisone plus Vitamin D (colecalciferol) supplementation; both arms followed by 6 cycles of conventional immunochemotherapy (R-CHOP or R-miniCHOP). Prednisone product details in Part I: PREDNISONE (product listing) with max daily dose 50 mg; Colecalciferol listed as oral vitamin D (product listing).
Target Sample Size
430

Eligibility

Recruits 430 Population includes adults age ≥ 65 years; isVulnerablePopulationSelected: false. Consent requirement: "Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures"..

Vulnerable Population
Population includes adults age ≥ 65 years; isVulnerablePopulationSelected: false. Consent requirement: "Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures".

Inclusion criteria

  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Adequate hematological counts defined as follows: - Absolute Neutrophil count (ANC) > 1.5 x 10^9/L unless due to bone marrow involvement by lymphoma - Platelet count ≥ 80.000/mm3 unless due to bone marrow involvement by lymphoma"}
  • {"criterion_text":"- Adequate renal function defined as follows: - Creatinine ≤ 2 mg/dL, unless secondary to lymphoma"}
  • {"criterion_text":"- Adequate hepatic function defined as follows: - Bilirubin ≤ 2 mg/dL unless secondary to lymphoma"}
  • {"criterion_text":"- LVEF > 40% at bidimensionally echocardiogram"}
  • {"criterion_text":"- Life expectancy ≥ 6 months"}
  • {"criterion_text":"- Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures"}
  • {"criterion_text":"- Subject must be able to adhere to the study visit schedule and other protocol requirements"}
  • {"criterion_text":"- Men must agree to use one of the below reported acceptable method of contraception (for themselves or female partners if WOCBP) 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. Acceptable methods for birth control, to be adopted even if male is surgically sterilized (i.e., status post vasectomy) are: - practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of immunochemotherapy, or - agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner] and withdrawal are not acceptable methods of contraception)"}
  • {"criterion_text":"- Age ≥ 65 years"}
  • {"criterion_text":"- Simplified Geriatric Assessment (sGA) performed at baseline, before start of any treatment."}
  • {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤3"}
  • {"criterion_text":"- Eligibility for 6 cycle treatment of anthracycline containing regimen (R-CHOP or R-miniCHOP)"}
  • {"criterion_text":"- No previous treatment for DLBCL or Follicular grade IIIb lymphoma"}
  • {"criterion_text":"- Ann Arbor stage I-IV"}
  • {"criterion_text":"- At least one site of measurable nodal disease at baseline ≥ 1.5 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan cannot be performed); or one metabolic active site of disease at baseline FDG-PET scan"}
  • {"criterion_text":"- Baseline Vitamin D [25(OH)VitD] serum level ≤ 40 ng/ml"}

Exclusion criteria

  • {"criterion_text":"- 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)"}
  • {"criterion_text":"- Use of VitD supplementation as standard of care at dose higher than 10,000 U/week (or higher than 2,000 U/day)."}
  • {"criterion_text":"- Suspect or clinical evidence of CNS involvement by lymphoma."}
  • {"criterion_text":"- Contraindication to the use of rituximab."}
  • {"criterion_text":"- Localized stage patients candidates for 3-4 cycles of R-CHOP/R-miniCHOP +RT."}
  • {"criterion_text":"- Contraindication to the use of VitD supplementation (Hypercalcemia/Hyperphosphatemia)."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: - Uncontrolled and/or active systemic infection (viral, bacterial or fungal) - Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Progression-Free Survival (PFS).","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Overall Survival (OS).","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Event Free Survival (EFS).","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Response rate (ORR, CRR; Cheson 2014).","definition_or_measurement_approach":"Measured as ORR and CRR according to Cheson 2014 criteria."}
  • {"endpoint_text":"- Early death rate (EDR): all deaths recorded within 90 days from the date of diagnosis.","definition_or_measurement_approach":"All deaths recorded within 90 days from the date of diagnosis."}
  • {"endpoint_text":"- AEs rate (CTCAE current version).","definition_or_measurement_approach":"Adverse events measured using current version of CTCAE."}
  • {"endpoint_text":"- Rate of ECOG changes after prephase.","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Rate of 25(OH)VitD correction (VitD supplementation arm): number of patients with 25(OH)VitD levels above or equal 20ng/ml at day 1 of cycle 2.","definition_or_measurement_approach":"Number of patients with 25(OH)VitD ≥ 20 ng/ml at day 1 of cycle 2 in the VitD supplementation arm."}
  • {"endpoint_text":"- Rate of patients who maintain 25(OH)VitD levels in the normal range at EOI.","definition_or_measurement_approach":"Proportion of patients maintaining 25(OH)VitD within normal range at End Of Induction (EOI)."}
  • {"endpoint_text":"- PROs endpoints include: time-to-deterioration in EORTC QLQ-C30 physical functioning and fatigue and FACT-Lym-LymS; proportion of patients in each arm achieving meaningful improvement in EORTC-QLQ-C30 physical functioning and fatigue, and FACT-Lym-LymS; and a comparison of EORTC-QLQ-C30 treatment-related symptoms between the two treatment arms.","definition_or_measurement_approach":"Patient-reported outcomes measured using EORTC-QLQ-C30 and FACT-Lym-LymS; includes time-to-deterioration, proportion achieving meaningful improvement, and comparison of treatment-related symptoms between arms."}

Recruitment

Planned Sample Size
430
Recruitment Window Months
65
Consent Approach
Informed consent must be provided by the subject: "Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures". Subject information sheets and consent forms are provided (multiple L1/L2 documents listed); translations include Italian (public title translations present). No assent process for minors (study population age ≥65).

Geography

Total Number Of Sites
45
Total Number Of Participants
430

Italy

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
18-11-2024
Processing Time Days
90
Number Of Sites
45
Number Of Participants
430

Sites

Site Name
Azienda Sanitaria Locale Della Provincia Di Barletta Andria Trani
Department Name
Ematologia - "Ospedale "Monsignor Raffaele Dimiccoli"
Contact Person Name
Giuseppe Tarantini
Contact Person Email
giuseppetarantini0@gmail.com
Site Name
Azienda Sanitaria Locale Della Provincia Di Biella
Department Name
S.C. Oncologia - Ospedale Degli Infermi
Contact Person Name
Annarita Conconi
Site Name
AORN San Giuseppe Moscati Avellino
Department Name
U.O.C. di Ematologia
Contact Person Name
Sonya De Lorenzo
Contact Person Email
sonya.delorenzo@tin.it
Site Name
ARNAS G. Brotzu
Department Name
SC Ematologia e CTMO - Ospedale Businco
Contact Person Name
Sara Veronica Usai
Contact Person Email
sara.v.usai@aob.it
Site Name
Centro Di Riferimento Oncologico Di Aviano
Department Name
S.O.C. Oncologia Medica A
Contact Person Name
Michele Spina
Contact Person Email
mspina@cro.it
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
Ematologia
Contact Person Name
Alessandra Tuccu
Site Name
Careggi University Hospital
Department Name
Unità funzionale di Ematologia
Contact Person Name
Benedetta Puccini
Site Name
Ssd Ematologia ASLTO4
Department Name
S.S.D. Ematologia - Ospedali Riuniti del Canavese - ASL TO4 Ospedale di Ciriè Chivasso e Ivrea
Contact Person Name
Chiara Ciochetto
Contact Person Email
cciochetto@aslto4.piemonte.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Ematologia - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
Contact Person Name
Costantino Riemma
Contact Person Email
costantino.riemma@irst.emr.it
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
SCDU Ematologia
Contact Person Name
Gianluca Gaidano
Contact Person Email
gianluca.gaidano@med.uniupo.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Ematologia
Contact Person Name
Ramona Cassin
Site Name
Azienda Ulss 3 Serenissima
Department Name
U.O. Ematologia - Ospedale Dell’ Angelo
Contact Person Name
Renato Bassan
Contact Person Email
bassanre@gmail.com
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Ematologia
Contact Person Name
Ivana Casaroli
Site Name
Azienda Sanitaria Locale Di Pescara
Department Name
UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi - P.O. Spirito Santo di Pescara
Contact Person Name
Elsa Pennese
Contact Person Email
elsa.pennese@asl.pe.it
Site Name
Azienda Unita Sanitaria Locale Di Piacenza
Department Name
U.O. Ematologia - Ospedale Guglielmo da Saliceto
Contact Person Name
Annalisa Arcari
Contact Person Email
a.arcari@ausl.pc.it
Site Name
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Department Name
Ematologia
Contact Person Name
Salvatrice Mancuso
Contact Person Email
salvatrice.mancuso@unipa.it
Site Name
Azienda Ospedaliera Regionale San Carlo
Department Name
U.O. Ematologia - A.O.R. "San Carlo"
Contact Person Name
Michele Cimminiello
Contact Person Email
miki-doc@virgilio.it
Site Name
Hospital Santa Maria Della Misericordia
Department Name
Ematologia
Contact Person Name
Leonardo Flenghi
Site Name
Azienda Sanitaria Locale Di Salerno
Department Name
U.O. Onco-ematologia, Presidio ospedaliero "A. TORTORA"
Contact Person Name
Catello Califano
Contact Person Email
c.califano@aslsalerno.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
Div. di Ematologia
Contact Person Name
Luca Arcaini
Contact Person Email
luca.arcaini@unipv.it
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
Ematologia
Contact Person Name
Francesco Merli
Contact Person Email
merli.francesco@ausl.re.it
Site Name
Azienda Ospedaliera S Giovanni Addolorata
Department Name
S.C. Ematologia - AO San Giovanni Addolorata
Contact Person Name
Erica Finolezzi
Contact Person Email
erica.finolezzi@gmail.com
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
U.O. di Ematologia -Ospedale degli Infermi di Rimini
Contact Person Name
Anna Merli
Contact Person Email
anna.merli@auslromagna.it
Site Name
Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
Department Name
Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare
Contact Person Name
Ombretta Annibali
Site Name
ASL Roma1
Department Name
Ematologia - ASL Roma 1 - Nuovo Regina Margherita - Osp. Santo Spirito -S. Filippo Neri
Contact Person Name
Tommaso Caravita Di Toritto
Contact Person Email
tommaso.caravita@aslroma1.it
Site Name
Istituto Di Ricovero E Cura A Carattere Scientifico Centro Di Riferimento Oncologico Della Basilicata
Department Name
UO di ematologia e Trapianto Cellule Staminali - IRCCS-Centro di Riferimento Oncologico
Contact Person Name
Giuseppe Pietrantuono
Contact Person Email
ematologia45@alice.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Ematologia - Ospedale delle Croci
Contact Person Name
Monica Tani
Contact Person Email
monica.tani@auslromagna.it
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Clinica di Ematologia - AOU Ospedali Riuniti
Contact Person Name
Guido Gini
Site Name
Azienda Sanitaria Territoriale Di Ascoli Piceno
Department Name
U.O.C. di Ematologia - Ospedale C. e G. Mazzoni
Contact Person Name
Piero Galieni
Contact Person Email
piero.galieni@sanita.marche.it
Site Name
Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo Alessandria
Department Name
S.C. Ematologia
Contact Person Name
Manuela Zanni
Contact Person Email
manuela.zanni@ospedale.al.it
Site Name
Azienda Ospedaliero-Universitaria Sant Andre
Department Name
Ematologia
Contact Person Name
Agostino Tafuri
Site Name
Azienda Ospedaliera S Maria Di Terni
Department Name
S.C. Oncoematologia
Contact Person Name
Anna Marina Liberati
Contact Person Email
marina.liberati@unipg.it
Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
U.O.C. Ematologia
Contact Person Name
Alberto Fabbri
Contact Person Email
fabbri7@unisi.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
Contact Person Name
Alice Di Rocco
Contact Person Email
dirocco@bce.uniroma1.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
S.C. Ematologia
Contact Person Name
Barbara Botto
Contact Person Email
bbotto@cittadellasalute.to.it
Site Name
San Camillo Forlanini Hospital
Department Name
Ematologia
Contact Person Name
Roberta Battistini
Site Name
Ospedale San Giovanni Bosco
Department Name
SSD di Ematologia e Malattie Trombotiche
Contact Person Name
Federica De Marco
Site Name
Azienda Sanitaria Universitaria Giuliano Isontina
Department Name
SC Ematologia
Contact Person Name
Francesco Zaja
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
Ematologia Universitaria
Contact Person Name
Federica Cavallo
Contact Person Email
f.cavallo@unito.it
Site Name
Azienda Ospedaliera Universitaria San Giovanni Di Dio E Ruggi d'Aragona
Department Name
U.O. Ematologia
Contact Person Name
Carmine Selleri
Contact Person Email
cselleri@unisa.it
Site Name
Casa Sollievo Della Sofferenza
Department Name
U.O. Ematologia - Casa Sollievo della Sofferenza
Contact Person Name
Potito Rosario Scalzulli
Contact Person Email
p.scalzulli@operapadrepio.it
Site Name
Universita Cattolica Del Sacro Cuore
Department Name
Ematologia
Contact Person Name
Stefan Hohaus
Contact Person Email
stefan.hohaus@Unicatt.it
Site Name
Ospedale Di Sassuolo S.p.A.
Department Name
Day Hospital Oncologico
Contact Person Name
Sara Bigliardi
Contact Person Email
s.bigliardi@ausl.mo.it
Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Department Name
SOC Clinica Ematologica
Contact Person Name
Jacopo Olivieri
Site Name
Azienda Unita Locale Socio Sanitaria N 8 Berica
Department Name
Ematologia - ULSS 8 Berica - Ospedale S. Bortolo
Contact Person Name
Maria Chiara Tisi

Sponsor

Primary sponsor

Full Name
Fondazione Italiana Linfomi Ets
Organisation Type
Patient organisation/association
Country Of Registered Address
Italy

Third parties

  • {"country":"","full_name":"FONDAZIONE GRADE ONLUS","duties_or_roles":"Monetary support","organisation_type":""}

Investigational products

Investigational Product Name
COLECALCIFEROL
Active Substance
Colecalciferol
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
No marketing authorisation number
Maximum Dose
25000 U unit(s) (max daily)
Investigational Product Name
PREDNISONE
Active Substance
Prednisolone
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
No marketing authorisation number
Maximum Dose
50 mg (max daily)
Combination Treatment
Yes

Related trials

Other published trials that may interest you.