Download PDF

Clinical Trial Results:
A randomized phase II multicenter study with a safety run-in to assess the tolerability and efficacy of the addition of oral selinexor (KPT-330) to standard induction chemotherapy in AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) in patients aged >= 66 years . A study in the frame of the masterprotocol of parallel randomized phase II studies in elderly AML

Summary
EudraCT number	2014-001876-75
Trial protocol	NL BE
Global end of trial date	19 Sep 2024

Results information
Results version number	v1(current)
This version publication date	03 Jan 2026
First version publication date	03 Jan 2026
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

HOVON103AMLSelinexor

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Other trial identifiers

EC number: MEC2015-521

Sponsor organisation name

HOVON

Sponsor organisation address

Dr. Molewaterplein 40, Rotterdam, Netherlands,

Public contact

HOVON Data Center, Erasmus MC Cancer Institute, Clinical Trial Center, +31 107041560, hdc@erasmusmc.nl

Scientific contact

HOVON Data Center, Erasmus MC Cancer Institute, Clinical Trial Center, +31 107041560, hdc@erasmusmc.nl

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Dec 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

28 Dec 2023

Global end of trial reached?

Yes

Global end of trial date

19 Sep 2024

Was the trial ended prematurely?

Yes

Main objective of the trial

For part A of the study (if applicable): 1. To assess the safety and tolerability of selinexor added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) and select the feasible dose level for part B 2. To assess in a randomized comparison the effect of selinexor on the CR rate. For part B: 1. To assess the safety and tolerability of selinexor added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) as regards the selected dose level of selinexor 2. To assess in a randomized comparison the effect of selinexor on the CR rate.

Protection of trial subjects

Insurance and monitoring

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jul 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 53

Country: Number of subjects enrolled

Belgium: 17

Country: Number of subjects enrolled

Switzerland: 35

Worldwide total number of subjects

105

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

105

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

All subjects gave written informed consent and were screened according to the inclusion- and exclusion criteria

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Control group

Arm description

Arm type

Active comparator

Investigational medicinal product name

Daunomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Daunomycin Days 45mg/m2 3hr infusion on days 1,2,3

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Cytarabine 200mg/m2 continuous infusion(24hrs) on days 1 thru 7

Experimental

Arm description

Arm type

Experimental

Investigational medicinal product name

Daunomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Daunomycin Days 45mg/m2 3hr infusion on days 1,2,3

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Cytarabine 200mg/m2 continuous infusion(24hrs) on days 1 thru 7

Investigational medicinal product name

SELINEXOR

Investigational medicinal product code

KPT-330

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

60 or 80 mg twice weekly on days 1,3,8,10,15,17,22,24 In part A of the study selinexor is started at a dose level of 60 mg twice weekly orally. Decisions regarding dose escalation to 80 mg twice weekly of each cycle, continuation with current dose level or reducing the dose is based on the incidence of DLT (dose limiting toxicity: death within 30 days of start cycle I and before start of cycle II) and will be performed according to the rules defined in section 17. If the decision is made to escalate to 80mg, a discussion with the Selinexor drug provider must occur first in order to evaluate the decision based on the most current safety data.

Number of subjects in period 1	Control group	Experimental
Started	53	52
Completed	34	27
Not completed	19	25
Adverse reactions	6	4
Consent withdrawn by subject	1	1
Other	4	9
Lack of efficacy	8	11

Baseline characteristics

Top of page

Reporting group title

Overall period

Reporting group description

Reporting group values	Overall period	Total
Number of subjects	105	105
Age categorical
Units: Subjects
From 65-84 years	105	105
Age continuous
Units: years
median (full range (min-max))	69 (65 to 80)	-
Gender categorical
Units: Subjects
Female	37	37
Male	68	68

End points

Top of page

Reporting group title

Control group

Reporting group description

Reporting group title

Experimental

Reporting group description

Primary: Primary endpoint

Top of page

End point title

Primary endpoint ^[1]

End point description

End point type

Primary

End point timeframe

See publication

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: See attached chart/documents for results

End point values	Control group	Experimental
Number of subjects analysed	53	52
Units: Whole	53	52

Attachments

List of reported non-SAE's
List of reported SAE's
Statistical data section from publication

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events will be reported from the first study-related procedure until 30 days following the last protocol treatment or until the start of subsequent systemic therapy for the disease under study, if earlier.

Adverse event reporting additional description

Adverse events occurring after 30 days should also be reported if considered related to study drug. Grade 3 or 4 adverse events considered related to study drug must be followed until recovery or until 6 months after the last protocol treatment, whichever comes first.

Assessment type

Systematic

Dictionary name

CTCAE

Dictionary version

Reporting group title

Control group

Reporting group description

Reporting group title

Experimental

Reporting group description

Serious adverse events	Control group	Experimental
Total subjects affected by serious adverse events
subjects affected / exposed	21 / 51 (41.18%)	24 / 51 (47.06%)
number of deaths (all causes)	34	40
number of deaths resulting from adverse events
Vascular disorders
Vascular disorders
Additional description: All combined
subjects affected / exposed	1 / 51 (1.96%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Surgical and medical procedures
Additional description: All combined
subjects affected / exposed	1 / 51 (1.96%)	0 / 51 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
General disorders and administration site conditions
Additional description: All combined
subjects affected / exposed	1 / 51 (1.96%)	2 / 51 (3.92%)
occurrences causally related to treatment / all	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
Additional description: All combined
subjects affected / exposed	3 / 51 (5.88%)	3 / 51 (5.88%)
occurrences causally related to treatment / all	1 / 3	3 / 3
deaths causally related to treatment / all	0 / 1	2 / 2
Psychiatric disorders
Psychiatric disorders
Additional description: All combined
subjects affected / exposed	0 / 51 (0.00%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Investigations
Additional description: All combined
subjects affected / exposed	0 / 51 (0.00%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
Additional description: All combined
subjects affected / exposed	0 / 51 (0.00%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Cardiac disorders
Additional description: All combined
subjects affected / exposed	1 / 51 (1.96%)	2 / 51 (3.92%)
occurrences causally related to treatment / all	1 / 1	1 / 2
deaths causally related to treatment / all	1 / 1	1 / 2
Nervous system disorders
Nervous system disorders
Additional description: All combined
subjects affected / exposed	4 / 51 (7.84%)	4 / 51 (7.84%)
occurrences causally related to treatment / all	2 / 4	4 / 4
deaths causally related to treatment / all	2 / 3	1 / 1
Gastrointestinal disorders
Gastrointestinal disorders
Additional description: All combined
subjects affected / exposed	1 / 51 (1.96%)	3 / 51 (5.88%)
occurrences causally related to treatment / all	0 / 1	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Hepatobiliary disorders
Additional description: All combined
subjects affected / exposed	1 / 51 (1.96%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Renal and urinary disorders
Additional description: All combined
subjects affected / exposed	2 / 51 (3.92%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Infections and infestations
Additional description: All combined
subjects affected / exposed	11 / 51 (21.57%)	16 / 51 (31.37%)
occurrences causally related to treatment / all	9 / 11	16 / 18
deaths causally related to treatment / all	2 / 2	5 / 6
Metabolism and nutrition disorders
Metabolism and nutrition disorders
Additional description: All combined
subjects affected / exposed	0 / 51 (0.00%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Control group	Experimental
Total subjects affected by non serious adverse events
subjects affected / exposed	49 / 51 (96.08%)	50 / 51 (98.04%)
Vascular disorders
Vascular disorder
Additional description: All combined
subjects affected / exposed	11 / 51 (21.57%)	11 / 51 (21.57%)
occurrences all number	12	12
General disorders and administration site conditions
General disorders and administration site conditions
Additional description: All combined
subjects affected / exposed	16 / 51 (31.37%)	12 / 51 (23.53%)
occurrences all number	19	15
Immune system disorders
Immune system disorders
Additional description: All combined
subjects affected / exposed	4 / 51 (7.84%)	1 / 51 (1.96%)
occurrences all number	5	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
Additional description: All combined
subjects affected / exposed	7 / 51 (13.73%)	13 / 51 (25.49%)
occurrences all number	10	18
Psychiatric disorders
Psychiatric disorders
Additional description: All combined
subjects affected / exposed	3 / 51 (5.88%)	5 / 51 (9.80%)
occurrences all number	3	6
Investigations
Investigations
Additional description: All combined
subjects affected / exposed	20 / 51 (39.22%)	22 / 51 (43.14%)
occurrences all number	53	67
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
Additional description: All combined
subjects affected / exposed	3 / 51 (5.88%)	2 / 51 (3.92%)
occurrences all number	3	2
Cardiac disorders
Cardiac disorders
Additional description: All combined
subjects affected / exposed	5 / 51 (9.80%)	12 / 51 (23.53%)
occurrences all number	6	16
Nervous system disorders
Nervous system disorders
Additional description: All combined
subjects affected / exposed	0 / 51 (0.00%)	8 / 51 (15.69%)
occurrences all number	0	11
Blood and lymphatic system disorders
Blood and lymphatic system disorders
Additional description: All combined
subjects affected / exposed	38 / 51 (74.51%)	34 / 51 (66.67%)
occurrences all number	63	45
Eye disorders
Eye disorders
Additional description: All combined
subjects affected / exposed	9 / 51 (17.65%)	6 / 51 (11.76%)
occurrences all number	9	7
Gastrointestinal disorders
Gastrointestinal disorders
Additional description: All combined
subjects affected / exposed	40 / 51 (78.43%)	43 / 51 (84.31%)
occurrences all number	83	83
Hepatobiliary disorders
Hepatobiliary disorders
Additional description: All combined
subjects affected / exposed	4 / 51 (7.84%)	2 / 51 (3.92%)
occurrences all number	5	3
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
Additional description: All combined
subjects affected / exposed	25 / 51 (49.02%)	20 / 51 (39.22%)
occurrences all number	36	28
Renal and urinary disorders
Renal and urinary disorders
Additional description: All combined
subjects affected / exposed	5 / 51 (9.80%)	7 / 51 (13.73%)
occurrences all number	5	8
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
Additional description: All combined
subjects affected / exposed	3 / 51 (5.88%)	6 / 51 (11.76%)
occurrences all number	3	7
Infections and infestations
Infections and infestations
Additional description: All combined
subjects affected / exposed	31 / 51 (60.78%)	28 / 51 (54.90%)
occurrences all number	66	63
Metabolism and nutrition disorders
Metabolism and nutrition disorders
Additional description: All combined
subjects affected / exposed	30 / 51 (58.82%)	32 / 51 (62.75%)
occurrences all number	90	98

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

04 Sep 2017

Amendment 1 The reason for this amendment is that the protocol and ICF have been modified following several updates of the Investigator Brochure. In addition, after reviewing the reported side effects, we have decided that the extensive eye examination is no longer mandatory, except when clinically necessary. We have also added the missing CVs and/or research statements for several participating centers. A memo announcing the official start date of the study has also been added.

26 Jan 2018

Amendment 2 The reason for this amendment is that two centers have been added for participation and that there are updates to the IMPD.

06 Aug 2018

Amendment 3 The reason for this change is: IMPD update

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/35869267

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

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Primary endpoint

Primary: Primary endpoint

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

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