Clinical Trials Register

Summary
EudraCT Number:	2018-002115-96
Sponsor's Protocol Code Number:	SCC215/P002900
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-01-17
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-002115-96

A.3

Full title of the trial

Optimizing MATRix as remission induction in PCNSL: De-escalated induction treatment in newly diagnosed primary CNS lymphoma – a randomized phase III trial

Ottimizzazione della combinazione MATRix come induzione della remissione nel PCNSL: trattamento di induzione ridotto nel linfoma primitivo del sistema nervoso centrale di nuova diagnosi – una sperimentazione di fase III randomizzata

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Optimizing MATRix, a combination of Methotrexate, Ara-C, Thiotepa and Rituximab given as an induction therapy, de-escalated in duration and total drug dose in comparison to the standard induction therapy and both treatments followed by a high dose therapy with autologous stem cell transplantation. The therapy is for patients with newly diagnosed primary lymphoma of the central nervous system.

Confronto tra la terapia di induzione standard MATRix, combinazione dei farmaci Metotrexato, Citarabina, Tiotepa e Rituximab, e una terapia di induzione con durata e dosaggio totale dei farmaci ridotti. Entrambi i trattamenti sono seguiti da una terapia ad alte dosi e trapianto di cellule staminali del paziente. Questa terapia è indicata per i pazienti con linfoma primario del sistema nervoso centrale di nuova diagnosi.

A.3.2

Name or abbreviated title of the trial where available

OptiMATe

A.4.1

Sponsor's protocol code number

SCC215/P002900

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04931368

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	CITY OF STUTTGART, REPRESENTED BY KLINIKUM STUTTGART
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Dipartimento Federale della Formazione e della Ricerca (BMBF/DLR)
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IELSG - International Extranodal Lymphoma Study Group
B.5.2	Functional name of contact point	Study Coordination Office
B.5.3	Address:
B.5.3.1	Street Address	Via Vincenzo Vela 6
B.5.3.2	Town/ city	Bellinzona
B.5.3.3	Post code	6500
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	0041586667321
B.5.5	Fax number	000000000000
B.5.6	E-mail	ielsg@ior.usi.ch

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tiotepa
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TIOTEPA
D.3.9.1	CAS number	52-24-4
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB10985MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Busulfano
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BUSULFANO
D.3.9.1	CAS number	55-98-1
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB05993MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Carmustina
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CARMUSTINA
D.3.9.1	CAS number	154-93-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	BCNU
D.3.9.4	EV Substance Code	SUB06132MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Citarabina
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CITARABINA
D.3.9.1	CAS number	147-94-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Ara-C
D.3.9.4	EV Substance Code	SUB06880MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 to 100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rituximab
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB12570MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 6
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Metotressato
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	metotrexato
D.3.9.1	CAS number	7413-34-5
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	MTX
D.3.9.4	EV Substance Code	SUB16442MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients diagnosed with primary central nervous system lymphoma (PCNSL)

Pazienti con diagnosi di linfoma primitivo del sistema nervoso centrale (PCNSL)

E.1.1.1

Medical condition in easily understood language

Patients with lymphoma originating in the central nervous system

Pazienti con linfoma originato nel sistema nervoso centrale

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10007953
E.1.2	Term	Central nervous system lymphoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate superiority of a de-escalated induction treatment strategy followed by autologous stem cell transplantation compared to the standard MATRix protocol in terms of event free survival (EFS)

Dimostrare la superiorità di una strategia di trattamento di induzione ridotto seguita da trapianto di cellule staminali autologhe rispetto al protocollo MATRIx standard in termini di sopravvivenza libera da eventi (EFS)

E.2.2

Secondary objectives of the trial

To compare overall survival, progression free survival, remission rate after consolidation, complication rate, neurocognitive impairment and quality of life between both treatment arms

Confrontare la sopravvivenza globale, la sopravvivenza libera da progressione, il tasso di remissione prima e dopo il consolidamento, il tasso dei pazienti che raggiungono il consolidamento, il tasso di complicanze, la compromissione neurocognitiva e la qualità della vita in entrambi i bracci di trattamento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system.
2. Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status </=2.
3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy.
4. Disease exclusively located in the CNS.
5. At least one measurable lesion.
6. Previously untreated patients (previous surgery or ongoing steroid treatment admitted).
7. Negative pregnancy test.
8. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
9. Ability to understand the nature of the trial and the trial related procedures and to comply with them.

1. Pazienti immunocompetenti con nuova diagnosi di linfoma primitivo del sistema nervoso centrale (PCNSL)
2. Età 18-65 anni (qualsiasi ECOG) o 66-70 anni (con performance status ECOG </ = 2)
3. Diagnosi istologica o citologica del patologo del centro di linfoma a cellule B. Campione diagnostico ottenuto tramite biopsia stereotassica o chirurgica, valutazione citologica del liquido cerebrospinale o vitrectomia
4. Malattia localizzata esclusivamente nel sistema nervoso centrale
5. Presenza di almeno una lesione misurabile
6. Pazienti non trattati in precedenza (fatta eccezione per chirurgia precedente o uso concomitante di steroidi)
7. Test di gravidanza negativo
8. Consenso informato scritto ottenuto in accordo alle linee guida internazionali e alle disposizioni di legge locali, fornito dal paziente o da un legale rappresentante autorizzato nel caso il paziente sia temporaneamente legalmente incapace a causa della malattia
9. Capacità di comprendere la natura dello studio, le sue procedure e di rispettarle.

E.4

Principal exclusion criteria

1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
2. Systemic lymphoma manifestation (outside the CNS).
3. Primary vitreoretinal lymphoma or primary leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord
4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ or other kinds of cancer without evidence of disease for at least 5 years.
5. Previous Non-Hodgkin lymphoma at any time.
6. Inadequate renal function (clearance < 60 ml/min).
7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
8. Active hepatitis B or C disease.
9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study.
10. Clinically relevant third space fluid accumulation according to the investigator's discretion.
11. Hypersensitivity to study treatment or any component of the formulation.
12. Taking any medications that are likely to cause interactions with the study medication
13. Known or persistent abuse of medication, drugs or alcohol.
14. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
15. Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
16. Previous participation in this trial.
17. Persons who are in a relationship of dependency/ employment with the sponsor and/ or the investigator.
18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
19. Current or planned pregnancy, nursing period
20. For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.

1. Immunodeficienza congenita o acquisita compresa l'infezione da HIV e precedente trapianto di organi.
2. Localizzazioni sistemiche del linfoma al di fuori del sistema nervoso centrale
3. Linfoma oculare isolato o linfoma leptomeningeo primario senza coinvolgimento del parenchima cerebrale o del midollo spinale
4. Neoplasie pregresse o concomitanti, ad esclusione del carcinoma in situ rimosso chirurgicamente o di qualsiasi altra neoplasia in remissione da almeno 5 anni
5. Diagnosi pregressa di linfoma Non-Hodgkin (in qualunque momento)
6. Inadeguata funzionalità renale (clearance < 60 ml/min)
7. Inadeguata funzionalità midollare, cardiaca, polmonare o epatica secondo la decisione dello sperimentatore
8. Epatite B o C attiva
9. Trattamento concomitante con altri farmaci sperimentali o partecipazione a un trial clinico nei 30 giorni precedenti l’inizio dello studio
10. Accumulo di fluido nel terzo spazio clinicamente rilevante, a discrezione dello sperimentatore
11. Ipersensibilità al trattamento in studio o a qualsiasi componente incluso nella formulazione dei farmaci
12. Assunzione di farmaci potenzialmente in grado di causare interazioni con il trattamento in studio
13. Abuso noto o persistente di farmaci, droghe o alcool
14. Infezione attiva da COVID-19 o mancato rispetto delle norme igieniche più comuni relative alla pandemia di COVID-19
15. Pazienti legalmente incapaci che non possano comprendere la natura, il significato e le conseguenze della partecipazione allo studio e senza un rappresentante legale designato
16. Precedente partecipazione a questo studio.
17. Persone in relazione di dipendenza/impiegati dello sponsor e/o dello sperimentatore
18. Qualsiasi condizione familiare, sociologica o geografica che possa pregiudicare il rispetto del protocollo di studio durante il trattamento o nel periodo di follow-up.
19. Gravidanza o allattamento in corso o programmati.
20. Pazienti in età fertile che rifiutino l’adozione delle seguenti misure contraccettive durante lo studio: dispositivi intrauterini o contraccezione ormonale in combinazione con un metodo barriera.

E.5 End points

E.5.1

Primary end point(s)

Event-free survival

Sopravvivenza libera da eventi

E.5.1.1

Timepoint(s) of evaluation of this end point

Defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first

Calcolata dalla data di randomizzazione alla fine prematura del trattamento per qualsiasi causa, progressione o morte, a secondo di quale si verifica prima

E.5.2

Secondary end point(s)

Progression free survival (PFS); Remission prior to consolidation therapy - RA II; Remission after consolidation - 30 days after autologous stemcell transplantation (ASCT); Rate of patients reaching consolidation; Quality of life (QoL): EORTC QLQ-C30, EORTC QLQ-BN20; measured during screening period, at response assessment II after completion of induction treatment, 30 days after ASCT and thereafter every 12 months until end of follow-up; Overall survival (OS)

Sopravvivenza libera da progressione (PFS); Remissione prima della terapia di consolidamento - alla seconda valutazione della malattia; Remissione dopo consolidamento - 30 giorni dopo ASCT; Tasso di pazienti che raggiungono il consolidamento; Qualità della vita (QoL): EORTC QLQ-C30, EORTC QLQ-BN20; valutata durante il periodo di screening, alla fine del trattamento (30 giorno dopo ASCT) e successivamente ogni 12 mesi durante il follow-up; Sopravvivenza (OS)

E.5.2.1

Timepoint(s) of evaluation of this end point

Defined as time from randomization until disease progression, relapse or death from any cause; Determinated at RA II and divided in CR, uCR, PR, SD, PD according to IPCG criteria; 30 days after autologous stemcell transplantation (ASCT); Defined as obtaining at least the first dose of consolidation therapy, will be determined after the response assessment II (following 4 cycles of MATRix in the control arm and following 1 cycle of R/HD-MTX and 2 cycles of MATRix in the experimental arm); Performed at screening, RA II and with beginning of RA III every 12 months until end of follow-up; Defined as time from randomization until death from any cause

Calcolata dalla data di randomizzazione fino alla progressione della malattia, ricaduta o morte per qualsiasi causa; Determinata alla seconda valutazione della malattia e suddivisa in CR, uCR, PR, SD, PD secondo criteri IPCG; 30 giorni dopo il trapianto autologo di cellule staminali (ASCT); Definito come ottenimento di almeno della prima dose di terapia di consolidamento, sarà determinato dopo la valutazione della risposta II (dopo 4 cicli di MATRix nel braccio di controllo e dopo 1 ciclo di R/HD-MTX e 2 cicli di MATRix nel braccio sperimentale); Eseguito allo screening, seconda valutazione della malattia e con inizio della terza valutazione della malattia ogni 12 mesi fino alla fine del follow-up; Calcolato dalla data di randomizzazione fino alla morte per qualsiasi causa

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Trattamento standard di induzione Braccio A-braccio di controllo / Braccio B - braccio sperimentale

Induction Treatment Arm A control treatment / Arm B experimental treatment

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Austria

Germany

Italy

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

249

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients, who are temporarily legally not competent due to their disease, which is not unusual, may be included if he/she has an authorized legal representative. Usually the patients regain their competence after having started the treatment.

Pazienti che sono temporaneamente legalmente non competenti a causa della loro malattia. Possono essere inclusi se hanno un rappresentante legale autorizzato. Di solito i pazienti riacquistano la loro competenza dopo aver iniziato il trattamento.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

246

F.4.2.2

In the whole clinical trial

326

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Further annual control examinations are recommended, after the patient has finished the study treatment and the follow up period

Si raccomandano ulteriori controlli annuali dopo il completamento del trattamento e del follow up dello studio

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-15

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials