Clinical Trials Register

Summary
EudraCT Number:	2014-003893-17
Sponsor's Protocol Code Number:	SAKK36/13
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-12-15
Trial results	View 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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-003893-17

A.3

Full title of the trial

Combination of ibrutinib and bortezomib followed by ibrutinib maintenance to treat patients with relapsed and refractory mantle cell lymphoma; a multicenter Phase I/II trial

A.3.1

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

Combination of ibrutinib and bortezomib and maintenance with ibrutinib in patients with mantle cell lymphoma

Combinazione con ibrutinib e bortezomib e mantenimento con ibrutinib in pazienti affetti da linfoma mantellare

A.3.2

Name or abbreviated title of the trial where available

SAKK 36/13

A.4.1

Sponsor's protocol code number

SAKK36/13

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	SAKK
B.1.3.4	Country	Switzerland
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	Janssen Pharmaceuticals NV
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SAKK
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	Effingerstrasse 33
B.5.3.2	Town/ city	Berna
B.5.3.3	Post code	CH - 3008
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	0041315084162
B.5.5	Fax number	0041313899200
B.5.6	E-mail	Simon.Schaefer@sakk.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.2.1.1.1	Trade name	IMBRUVICA - 140 MG -CAPSULE RIGIDE -USO ORALE - FLACONE (HDPE) - 1 FLACONE (120 CAPSULE RIGIDE)
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.V.
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	Imbruvica
D.3.2	Product code	[JNJ-54179060]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ibrutinib
D.3.9.1	CAS number	936563-96-1
D.3.9.2	Current sponsor code	JNJ-54179060
D.3.9.3	Other descriptive name	Ibrutinib
D.3.9.4	EV Substance Code	SUB120863
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	140
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.2.1.1.1	Trade name	VELCADE - 1 FLACONCINO DA 3.5 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.V.
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	Velcade
D.3.2	Product code	[JNJ-26866138]
D.3.4	Pharmaceutical form	Powder for solution for injection
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	BORTEZOMIB
D.3.9.1	CAS number	179324-69-7
D.3.9.2	Current sponsor code	JNJ-26866138
D.3.9.3	Other descriptive name	Bortezomib
D.3.9.4	EV Substance Code	SUB20020
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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

Mantle ell lymphoma

Linfoma mantellare

E.1.1.1

Medical condition in easily understood language

Mantle cell lymphoma

Linfoma mantellare

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10026806
E.1.2	Term	Mantle zone lymphoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the phase II is to define the efficacy of ibrutinib in combination with bortezomib in patients with relapsed or refractory MCL.

L'obiettivo primario della fase II ¿ definire l'efficacia di ibrutinib in combinazione con bortezomib in pazienti con MCL recidivo o refrattario

E.2.2

Secondary objectives of the trial

- to determine the safety and tolerability of the RP2D of ibrutinib in combination with bortezomib
- to determine the efficacy of ibrutinib in combination with bortezomib in patients with relapsed MCL followed by an ibrutinib maintenance therapy.

- determinare la sicurezza e la tollerabilit¿ della dose di ibrutinib raccomandata per la fase II in combinazione con bortezomib
- determinare l'efficacia di ibrutinib in combinazione con bortezomib in pazienti con MCL recidivo seguita da una terapia di mantenimento con ibrutinib.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Mantle cell lymphoma with either overexpression of cyclin D1 protein or evidence of t
- Refractory or relapsed LCM after pretreatment with nonbortezomib-containing chemotherapy
- At least one measurable lesion =11 mm (greatest transverse diameter) measured with CT scan or MRI
- Adequate hematological values, hepatic and renal function
- Effective method of birth control in women of childbearing potential and men who are sexually active
- Negative pregnancy test in women of childbearing potential; breastfeeding women are ineligible for this trial

• Linfoma mantellare (LCM) con sovra-espressione della ciclina D1 o con documentazione di t(11;14)
• LCM refrattario o recidivante dopo precedente trattamento con chemioterapia non comprendente il bortezomib
• Almeno una lesione misurabile =11 mm (diametro trasversale maggiore) con TAC o RMN
• Valori ematici, funzione epatica e renale adeguati
• Efficace contraccezione nelle donne in età fertile e negli uomini sessualmente attivi.
• Test di gravidanza negativo nelle donne in età fertile; le donne in allattamento non possono partecipare

E.4

Principal exclusion criteria

- Prior therapy with ibrutinib or bortezomib
- Actual or prior presence of the disease in the CNS
- Exclusion of the following prior treatments prior to trial registration
o major surgery within 4 weeks
o concurrent treatment with other experimental drugs or treatment in a clinical trial within
30 days.
o treatment with chemotherapy and radiotherapy within 3 weeks
o vaccinated with live, attenuated vaccines within 4 weeks
- History of stroke or intracranial hemorrhage within 6 months prior to trial registration
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists
- Requires treatment with strong or moderate CYP3A inhibitors
- Prior allogeneic bone marrow or solid organ transplantation

• Precedente terapia con ibrutinib e bortezomib
• Attuale o pregresso focolaio della malattia nel sistema nervoso centrale
• Esclusione dei seguenti trattamenti prima della registrazione
¿ Interventi di chirurgia maggiore nelle 4 settimane precedenti
¿ Concomitante trattamento con medicamenti sperimentali o in uno studio clinico nelle 4 settimane precedenti
¿ Chemioterapie o irradiazioni nelle 3 settimane precedenti
¿ Vaccinazioni con vaccini vivi attenuati, nelle 4 settimane precedenti
• Storia di ictus o sanguinamento intracranico nei 6 mesi precedenti l'inizio dello studio
• Assunzione di anticoagulanti (warfarin o simili antagonisti della vitamina K)
• Necessità di trattamento con inibitori forti o moderati del CYP3A
• Pregresso trapianto allogenico di midollo osseo o di organo

E.5 End points

E.5.1

Primary end point(s)

Overall response (OR) (combination therapy)

Tasso di risposta alla terapia in terapia combinata

E.5.1.1

Timepoint(s) of evaluation of this end point

Cycles 1-6

Cicli 1-6

E.5.2

Secondary end point(s)

Adverse Events; Overall response (OR) during trial treatment; Progression-free survival (PFS); Time to treatment failure; Duration of objective response

Eventi avversi; Tasso di risposta alla terapia durante il trattamento in studio; Sopravvivenza senza progressione ; Tempo al fallimento della terapia; Durata della risposta oggettiva alla terapia

E.5.2.1

Timepoint(s) of evaluation of this end point

During Trial treatment; During Trial treatment; Time from registration until progression of disease or death; From registration until treatment failure; Time from first observation of CR, CRu or PR until documentation of progression, or relapse
thereafter

In corso di trattamento in studio; In corso di trattamento in studio; Dalla registrazione fino a progressione della malattia o decesso; Dalla registrazione fino al fallimento del trattamento; Tempo dalla prima osservazione di CR, CRu o PR fino alla documentazione di progressione o recidiva

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase I/II

Fase I/II

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

Germany

Italy

Switzerland

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:

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

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

F.4.2.2

In the whole clinical trial

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)

Patients will be treated according to the local clinical practice

I pazienti saranno trattati in accordo alla pratica clinica locale

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

2018-03-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-12-13

P. End of Trial
P.	End of Trial Status	Completed

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