Clinical Trials Register

Summary
EudraCT Number:	2016-003094-18
Sponsor's Protocol Code Number:	KCP-330-012
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-12-22
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

Germany - BfArM

A.2

EudraCT number

2016-003094-18

A.3

Full title of the trial

A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-Dose Dexamethasone (Sd) in Patients with Multiple Myeloma Previously Treated with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and Daratumumab, and Refractory to Prior Treatment with Glucocorticoids, an Immunomodulatory Agent, a Proteasome Inhibitor, and the anti-CD38 mAb Daratumumab

A.3.1

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

A Study of Selinexor (KPT-330) Plus Low-Dose Dexamethasone in Previously Treated Patients with Multiple Myeloma

A.3.2

Name or abbreviated title of the trial where available

STORM

A.4.1

Sponsor's protocol code number

KCP-330-012

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02336815

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	Karyopharm Therapeutics Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Karyopharm Therapeutics Inc.
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	Karyopharm Therapeutics Inc.
B.5.2	Functional name of contact point	Clinical Trials Information Desk
B.5.3	Address:
B.5.3.1	Street Address	85 Wells Ave
B.5.3.2	Town/ city	Newton
B.5.3.3	Post code	MA 02459
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrials@karyopharm.com

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/14/1355
D.3 Description of the IMP
D.3.1	Product name	Selinexor
D.3.2	Product code	KPT-330
D.3.4	Pharmaceutical form	Film-coated 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.3.9.1	CAS number	1393477-72-9
D.3.9.2	Current sponsor code	KPT-330
D.3.9.3	Other descriptive name	SELINEXOR
D.3.9.4	EV Substance Code	SUB177942
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.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	Germany
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	Dexamethasone
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	DEXAMETHASONE
D.3.9.1	CAS number	50-02-2
D.3.9.3	Other descriptive name	Dexamethasone
D.3.9.4	EV Substance Code	SUB07017MIG
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	4
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

Refractory multiple myeloma (RMM)

E.1.1.1

Medical condition in easily understood language

multiple myeloma

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10028228
E.1.2	Term	Multiple myeloma
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

Evaluate the efficacy (overall response rate [ORR]) for treatment with selinexor 80 mg plus low-dose dexamethasone (20 mg) (Sd) twice weekly (four-week cycles) in patients with MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab; and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab (herein referred to as penta-refractory MM).
ORR will include patients who experience partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), based on International Myeloma Working Group (IMWG) response criteria (Kumar 2016) for patients with pentarefractory MM in Part 2 (Expansion).

E.2.2

Secondary objectives of the trial

The following endpoints will be analyzed separately for (a) Part1 patients with quad-refractory MM, (b) Part1 patients with pentarefractory MM, and (c) Part2 (expansion) patients with penta-refractory MM. Additionally, analyses of safety and tolerability will be performed on the overall population of patients from Parts1 and2 who received at least one dose of study treatment.
- Duration of response
- Clinical Benefit Rate and duration of clinical benefit (Duration from first observation of at least MR to time of disease progression or death due to disease progression, whichever occurs first.
- Disease Control Rate
- Progression Free Survival
- Time to Progression obtained with selinexor plus dexamethasone vs. TTP on most recent prior therapy
- Time to next treatment
- Overall Survival
- Quality of Life
- Safety and tolerability
- Describe the PK properties of selinexor in this patient population (Part1 only)
Exploratory objectives
For details see page 40 of study protocol

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent in accordance with federal, local, and institutional guidelines.
2. Age ≥ 18 years at the time of signing informed consent.
3. Measurable MM based on IMWG guidelines as defined by at least one of the following:
a. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA b. Urinary M-protein excretion ≥ 200 mg/24 hours
c. FLC ≥ 100 mg/L, provided that the FLC ratio is abnormal.
d. If serum protein electrophoresis is felt to be unreliable for routine Mprotein measurement, then quantitative Ig levels by nephelometry is acceptable.
4. Patients must have previously received ≥ 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/exclusion criteria are met.
5. MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
6. Multiple myeloma that is refractory to the patient's most recent anti- MM regimen. (Documented severe intolerance to the patient's last therapy is allowed upon approval by the Medical Monitor.)
7. Any clinically significant non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #17) that patients experienced from treatments in previous clinical studies must have resolved to Grade ≤2 by Cycle 1 Day 1.
8. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.
9. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine clearance of ≥ 20 mL/min, calculated using the formula of Cockroft and Gault.
10. Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose of study treatment.
11. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
12. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets):
a. Total WBC count ≥ 1,000/mm3
b. ANC ≥ 1000/mm3
c. Platelet count ≥ 75,000/mm3 (patients in whom <50% of bone marrow nucleated cells are plasma cells) or ≥ 50,000/mm3 (patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells. [Platelet transfusions <1 week prior to Cycle 1 Day 1 are prohibited (see below).]
13. Hemoglobin level ≥ 8.5 g/dL. In certain cases, patients with stable baseline hemoglobin level >8.0 may be included following approval by the Medical Monitor. [Red blood cell transfusions <2 weeks prior to Cycle 1 Day 1 are prohibited (see below).]
14. Confirmation of patient eligibility for specific key criteria for study participation with the Medical Monitor.

E.4

Principal exclusion criteria

1. Active smoldering MM.
2. Active plasma cell leukemia.
3. Documented systemic amyloid light chain amyloidosis.
4. Active central nervous system (CNS) MM.
5. Pregnancy or breastfeeding.
6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1.
7. Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 Day 1
8. Life expectancy of < 4 months.
9. Major surgery within four weeks prior to Cycle 1 Day 1.
10. Active, unstable cardiovascular function:
a. Symptomatic ischemia, or
b. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
c. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or d. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1.
11. Active, uncontrolled hypertension.
12. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose.
13. Known HIV seropositive.
14. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen).
15. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to enrollment. Cancer treated with curative intent > 5 years previously and without evidence of recurrence will be allowed.
16. Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
17. Grade ≥ 3 peripheral neuropathy, and Grade ≥ 2 painful neuropathy, within 21 days prior to Cycle 1 Day 1.
18. Serious, active psychiatric or medical conditions which, in the opinion of the Investigator, could interfere with treatment.
19. Participation in an investigational anti-cancer study within 21 days prior to Cycle 1 Day 1.
20. Receipt of transfusions as follows:
a. Platelet infusion within 1 week prior to Cycle 1 Day 1.
b. RBC transfusion within 2 weeks prior to Cycle 1 Day 1.
21. Receipt of the following blood growth factors within 2 weeks prior to Cycle 1 Day 1: Granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), erythropoietin (EPO), or megakaryocyte growth factor.
22. Known intolerance to or contraindication for glucocorticoid therapy at Cycle 1 Day 1.
23. Prior exposure to a SINE compound, including Selinexor.
24. Unable or unwilling to comply with protocol requirements, including providing a 24-hour urine samples at the required study time points.

E.5 End points

E.5.1

Primary end point(s)

Overall Response Rate (ORR)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary statistical analysis of efficacy will be performed on ORR (achievement of PR, VGPR, CR or sCR) for the mITT population after the last patient has completed 1 cycle.

E.5.2

Secondary end point(s)

Duration of response; clinical benefit rate and duration of clinical benefit; disease control rate; progression free survival; time to progression obtained with selinexor plus
dexamethasone versus TTP on most recent prior therapy; Time to Next Treatment (TTNT = Duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first), overall survival; quality of life using FACT-MM.

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary analysis of efficacy will be performed after the last patient has completed 1 cycle.

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

Yes

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

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

Belgium

France

Germany

Greece

United States

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

The End of Study (EoS) will occur when all patients have completed the one-year Follow-up Period (i.e., when the last patient has expired, been followed for 12 months after last dose of study drug, been lost to follow-up, or has withdrawn consent, whichever occurs first).

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

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:

130

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

210

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)

After a patient has ceased his/her participation in the study, his/her medical doctor will offer the most appropriate treatment currently available.

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

2017-06-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-05-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-07-26

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