Clinical Trials Register

Summary
EudraCT Number:	2014-002444-40
Sponsor's Protocol Code Number:	EMC-MM-KPT-330-001
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-10-14
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

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2014-002444-40

A.3

Full title of the trial

A Phase II study of Selinexor (KPT-330) combined with bortezomib and dexamethasone (SVd) for induction and consolidation for patients with progressive or refractory Multiple Myeloma.

Inductie en consolidatie behandeling met selinexor gecombineerd met bortezomib en dexamethason voor patiënten met Multipel Myeloom met verslechtering van het ziektebeeld.

A.3.1

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

A Phase II study of Selinexor (KPT-330) combined with bortezomib and dexamethasone (SVd) for induction and consolidation for patients with progressive or refractory Multiple Myeloma.

Inductie en consolidatie behandeling met selinexor gecombineerd met bortezomib en dexamethason voor patiënten met Multipel Myeloom met verslechtering van het ziektebeeld.

A.3.2

Name or abbreviated title of the trial where available

SVd

A.4.1

Sponsor's protocol code number

EMC-MM-KPT-330-001

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	Erasmus MC
B.1.3.4	Country	Netherlands
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	karyopharm
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Erasmus MC
B.5.2	Functional name of contact point	Sarah Lonergan
B.5.3	Address:
B.5.3.1	Street Address	's gravendijkwal 230
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3015 CE
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31107034546
B.5.5	Fax number	+31107033703
B.5.6	E-mail	s.lonergan@erasmusmc.nl

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	Velcade
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen Cilag SpA
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	bortezomib
D.3.2	Product code	1000268
D.3.4	Pharmaceutical form	Powder and solution for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	No
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	selinexor (25 mg)
D.3.2	Product code	KPT-330
D.3.4	Pharmaceutical form	Tablet
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	selinexor
D.3.9.2	Current sponsor code	KPT-330
D.3.9.3	Other descriptive name	KPT-330
D.3.9.4	EV Substance Code	SUB168135
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	25
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	No
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	selinexor (10mg)
D.3.2	Product code	KPT-330
D.3.4	Pharmaceutical form	Tablet
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	selinexor
D.3.9.2	Current sponsor code	KPT-330
D.3.9.3	Other descriptive name	KPT-330
D.3.9.4	EV Substance Code	SUB168135
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	10
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	No
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	selinexor (20mg)
D.3.2	Product code	KPT-330
D.3.4	Pharmaceutical form	Tablet
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	selinexor
D.3.9.2	Current sponsor code	KPT-330
D.3.9.3	Other descriptive name	KPT-330
D.3.9.4	EV Substance Code	SUB168135
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	20
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

A Phase II study of Selinexor (KPT-330) combined with bortezomib and dexamethasone (SVd) for induction and consolidation for patients with progressive or refractory Multiple Myeloma.

Inductie en consolidatie behandeling met selinexor gecombineerd met bortezomib en dexamethason voor patiënten met Multipel Myeloom met verslechtering van het ziektebeeld.

E.1.1.1

Medical condition in easily understood language

Patients with symptomatic Multiple Myeloma who are progressive or who were refractory to their first line regimen

Patiënten met symptomatisch multipel myeloom die zijn progressief of die refractair waren voor hun eerste lijn behandeling

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the safety and tolerability of selinexor at 3 different dose levels in combination with bortezomib/dexamethasone & determine the recommended dose level (RDL) of selinexor for Part II

Het doel van dit onderzoek is om de veiligheid en effectiviteit van selinexor in combinatie met bortezomib en een lage dosis dexamethason te onderzoeken en te zien of uw ziekte verbetert met deze behandeling.

E.2.2

Secondary objectives of the trial

• Evaluate the response (sCR, CR, VGPR, PR) after 8 cycles of selinexor, bortezomib and dexamethasone.

respons evaluatie (SCR, CR, VGPR, PR) na 8 cycli van selinexor, bortezomib en dexamethason.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Documented diagnosis of multiple myeloma and measurable disease (serum M-protein ≥ 5 g/L or urine M-protein ≥ 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/L);
• Documented progression as per the IMWG uniform response criteria (Durie, 2006) during or after the anti-myeloma regimen; or never achieved a response better than PD after at least 2 cycles of their previous anti-myeloma regimen.

• Gedocumenteerde diagnose van multiple myeloom en meetbare ziekte (serum M-proteïne ≥ 5 g / L of urine M-proteïne ≥ 200 mg/24 uur of abnormale FLC verhouding met betrokken vrije lichte keten (FLC)> 100 mg / L);
• gedocumenteerde progressie volgens de IMWG uniforme respons criteria (Durie, 2006) tijdens of na de anti-myeloom regime; of nooit een respons verkregen beter dan PD na minimaal 2 cycli van de vorige anti-myeloma regime.

E.4

Principal exclusion criteria

• Prior resistance/refractory disease to bortezomib
• Systemic AL amyloidosis
• Non secretory myeloma
• Known CNS involvement
• Absolute neutrophil count (ANC) <1.0 x 109/L, unless related to MM.
• Platelet count < 50 x 109/L.
• Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L).
• Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted).

Voorafgaand refractaire voor bortezomib
• Systemische AL amyloïdose
• Niet secretoire myeloma
• Bekende CNS betrokkenheid
• Absoluut aantal neutrofielen (ANC) <1,0 x 109 / L, tenzij gerelateerd aan MM.
• Aantal trombocyten <50 x 109 / L.
• gecorrigeerd serumcalcium> 14 mg / dl (> 3,5 mmol / L).
• Hemoglobine <8 g / dl (<4,9 mmol / L; voorafgaand RBC transfusie of recombinant humaan erytropoëtine gebruik is toegestaan).

E.5 End points

E.5.1

Primary end point(s)

• Dose-limiting toxicity (DLT) as defined in paragraph 4.1, and recommended phase II dose (RDL) of selinexor when combined with bortezomib and dexamethasone

Dosis-limit toxiciteit (DLT) zoals omschreven in paragraaf 4.1, en aanbevolen fase II dosis (RDL) van selinexor in combinatie met bortezomib en dexamethasone

E.5.1.1

Timepoint(s) of evaluation of this end point

in cycle 1, twice a month in all other cycles.
 After induction treatment cycle 2 and 4.
 After High-dose Melphalan and autologous stem cell transplantation (if applicable)
 After consolidation treatment cycle 2 and 4

E.5.2

Secondary end point(s)

• Toxicity

• Toxiciteit

E.5.2.1

Timepoint(s) of evaluation of this end point

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)

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.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

Patients can leave the study at any time for any reason if they wish to do so without any consequences. The investigator can decide to withdraw a patient from the study for urgent medical reasons. Specific criteria for withdrawal are:
• Death
• Excessive toxicity
• No compliance of the patient
• Refusal to continue protocol treatment
• Progression during treatment

Patiënten kunnen de studie te verlaten op elk moment en om welke reden dan ook als ze dat willen, zonder enige gevolgen. De onderzoeker kan beslissen om een patiënt uit de studie om medische redenen in te trekken. Specifieke criteria voor intrekking zijn:
• Dood
• toxiciteit
• Geen naleving van de patiënt
• Weigering protocol behandeling voort te zetten
• Progressie tijdens de behandeling

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

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)

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

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

During follow up every 2 months until progression. Thereafter every 6 months until 5
years after registration.

Tijdens de follow-up om de 2 maanden tot progressie. Vervolgens om de 6 maanden tot 5
jaar na registratie

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

2014-10-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-10-16

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

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