Clinical Trial Results:
A Cancer Research UK Phase I/IIa trial of AT9283 (a selective inhibitor of aurora kinases) given over 72 hours every 21 days via intravenous infusion in children and adolescents aged 6 months to 18 years with relapsed and refractory acute leukaemia.

Due to a system error, the data reported in v1 is not correct and has been removed from public view.

Summary
EudraCT number	2009-016952-36
Trial protocol	GB
Global end of trial date	01 Jul 2014

Results information
Results version number	v2(current)
This version publication date	05 Jun 2016
First version publication date	24 Jul 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set Data reviewed and corrected following EudraCT system downtime (July 2015 to January 2016).

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

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Trial information

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Sponsor protocol code

CR0708-12

ISRCTN number

US NCT number

NCT01431664

WHO universal trial number (UTN)

Sponsor organisation name

Cancer Research UK

Sponsor organisation address

407 St John Street, London, United Kingdom, EC1V 4AD

Public contact

Centre for Drug Development, Cancer Research UK, +44 02072420200, regquery@cancer.org.uk

Scientific contact

Centre for Drug Development, Cancer Research UK, +44 02072420200, regquery@cancer.org.uk

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

04 Dec 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

01 Jul 2014

Global end of trial reached?

Yes

Global end of trial date

01 Jul 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

To recommend a dose of AT9283 for Phase II evaluation in paediatric patients with acute leukaemia.

Protection of trial subjects

None

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Sep 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 7

Worldwide total number of subjects

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

85 years and over

Subject disposition

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Recruitment details

Study participants were enrolled from 14 September 2011 to 01 July 2014 in 4 clinical study centres in the UK.

Screening details

Patients were male or female aged 6 months to 18 years old, who had morphologically proven acute leukaemia (relapsed and refractory disease) with Karnofsky/Lansky play performance score of at least 50 and a life expectancy of at least 8 weeks.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1 (9.0 mg/m2/day)

Arm description

AT9283 9.0 mg/m2/day dose level.

Arm type

Experimental

Investigational medicinal product name

AT9283

Investigational medicinal product code

AT9283

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as a 72 hour intravenous infusion every 21 days (one treatment cycle).

Cohort 2 (14.5 mg/m2/day)

Arm description

AT9283 14.5 mg/m2/day dose level.

Arm type

Experimental

Investigational medicinal product name

AT9283

Investigational medicinal product code

AT9283

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as a 72 hour intravenous infusion every 21 days (one treatment cycle).

Cohort 3 (23.0 mg/m2/day)

Arm description

AT9283 23.0 mg/m2/day dose level.

Arm type

Experimental

Investigational medicinal product name

AT9283

Investigational medicinal product code

AT9283

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as a 72 hour intravenous infusion every 21 days (one treatment cycle).

Number of subjects in period 1	Cohort 1 (9.0 mg/m2/day)	Cohort 2 (14.5 mg/m2/day)	Cohort 3 (23.0 mg/m2/day)
Started	3	3	1
Completed	3	3	1

Baseline characteristics

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Reporting group title

Cohort 1 (9.0 mg/m2/day)

Reporting group description

AT9283 9.0 mg/m2/day dose level.

Reporting group title

Cohort 2 (14.5 mg/m2/day)

Reporting group description

AT9283 14.5 mg/m2/day dose level.

Reporting group title

Cohort 3 (23.0 mg/m2/day)

Reporting group description

AT9283 23.0 mg/m2/day dose level.

Reporting group values	Cohort 1 (9.0 mg/m2/day)	Cohort 2 (14.5 mg/m2/day)	Cohort 3 (23.0 mg/m2/day)	Total
Number of subjects	3	3	1	7
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)	1	1	0	2
Children (2-11 years)	1	1	1	3
Adolescents (12-17 years)	0	1	0	1
Adults (18-64 years)	1	0	0	1
Gender categorical
Units: Subjects
Female	1	0	1	2
Male	2	3	0	5

End points

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Reporting group title

Cohort 1 (9.0 mg/m2/day)

Reporting group description

AT9283 9.0 mg/m2/day dose level.

Reporting group title

Cohort 2 (14.5 mg/m2/day)

Reporting group description

AT9283 14.5 mg/m2/day dose level.

Reporting group title

Cohort 3 (23.0 mg/m2/day)

Reporting group description

AT9283 23.0 mg/m2/day dose level.

Subject analysis set title

All treated patients

Subject analysis set type

Full analysis

Subject analysis set description

All enrolled and eligible patients who received at least one dose of AT9283.

Primary: Recommended Dose of AT9283 for Phase IIb Evaluation

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End point title

Recommended Dose of AT9283 for Phase IIb Evaluation ^[1]

End point description

The biologically active dose of AT9283 and maximal dose of AT9283 at which no more than one out of up to six patients at that dose level experienced a probably or highly probably drug related dose limiting toxicity (DLT) during the first cycle of AT9283.

End point type

Primary

End point timeframe

First cycle of AT9283 administration.

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: All safety data were presented in a descriptive fashion, with adverse events reported for each dose level and presented by adverse event term by the worst grade observed.

End point values	All treated patients
Number of subjects analysed	7
Units: mg/m2/day
Maximum administered dose	23

No statistical analyses for this end point

Secondary: Safety

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End point title

Safety

End point description

The causality and severity grading of each adverse event (AE), according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE),Version 4.02. All AEs with a causality of possibly, probably or highly probably related to AT9283 were considered to indicate relatedness.

End point type

Secondary

End point timeframe

From patient consent to 28 days post last dose of AT9283.

End point values	All treated patients
Number of subjects analysed	7
Units: No. of AEs
All AEs	97
Related AEs	29
DLTs	0

No statistical analyses for this end point

Secondary: Response

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End point title

Response

End point description

Patients' disease was measured and characterised according to the following disease response criteria: Complete remission (CR) - absolute neutrophil count (ANC) ≥1.0x10^9/L; platelet count ≥100x10^9/L; bone marrow <5% blasts. Complete remission with incomplete bone marrow recovery (CRi) - ANC ≥0.75x10^9/L; platelet count ≥75x10^9/L; bone marrow <5% blasts. Partial remission (PR) - ANC ≥0.75x10^9/L; platelet count ≥75x10^9/L; bone marrow <25% blasts. and disease progression (PD).

End point type

Secondary

End point timeframe

From baseline until after 6 cycles.

End point values	All treated patients
Number of subjects analysed	7
Units: Number of subjects with a response
CR	0
CRi	0
PR	0
PD	7

No statistical analyses for this end point

Secondary: AT9283 Pharmacokinetic Profile

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End point title

AT9283 Pharmacokinetic Profile

End point description

Pharmacokinetic (PK) parameters: maximum concentration (Cmax), area under the time-concentration curve (AUC), half-life, clearance (Cl) and steady state volume of distribution (Vss).

End point type

Secondary

End point timeframe

Pre-treatment Day 1 through to Day 4 of Cycle 1.

End point values	Cohort 1 (9.0 mg/m2/day)	Cohort 2 (14.5 mg/m2/day)	Cohort 3 (23.0 mg/m2/day)
Number of subjects analysed	3	3	1
Units: ng/mL
arithmetic mean (standard deviation)
Cmax (ng/mL)	21.9 ( 16.9 )	37.5 ( 11.4 )	46 ( 0 )
AUC (ng/mL. hr)	990 ( 514 )	2268 ( 929 )	2766 ( 0 )
Half-life (hr)	5.3 ( 0.9 )	5.3 ( 1.1 )	5.3 ( 0 )
Cl (L/hr)	25.7 ( 12.8 )	23.1 ( 26 )	18.4 ( 0 )
Vss (L)	197 ( 125 )	180 ( 215 )	141.7 ( 0 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From patient consent to 28 days post last dose of AT9283.

Assessment type

Systematic

Dictionary name

NCI-CTCAE

Dictionary version

4.02

Reporting group title

Cohort 1 (9.0 mg/m2/day)

Reporting group description

AT9283 9.0 mg/m2/day dose level.

Reporting group title

All treatment cohorts

Reporting group description

All patients treated at the range of AT9283 dose levels administered.

Reporting group title

Cohort 3 (23.0 mg/m2/day)

Reporting group description

AT9283 23.0 mg/m2/day dose level.

Reporting group title

Cohort 2 (14.5 mg/m2/day)

Reporting group description

AT9283 14.5 mg/m2/day dose level.

Serious adverse events	Cohort 1 (9.0 mg/m2/day)	All treatment cohorts	Cohort 3 (23.0 mg/m2/day)	Cohort 2 (14.5 mg/m2/day)
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	5 / 7 (71.43%)	1 / 1 (100.00%)	1 / 3 (33.33%)
number of deaths (all causes)	0	1	1	0
number of deaths resulting from adverse events	0	0	0	0
Investigations
Neutrophil count decreased
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	2 / 2	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	1 / 3 (33.33%)	3 / 7 (42.86%)	1 / 1 (100.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	2 / 2	4 / 4	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders - other, specify
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death NOS
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 1 (100.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Nausea
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	2 / 2	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Bone pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Sepsis
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	2 / 2	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cohort 1 (9.0 mg/m2/day)	All treatment cohorts	Cohort 3 (23.0 mg/m2/day)	Cohort 2 (14.5 mg/m2/day)
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	7 / 7 (100.00%)	1 / 1 (100.00%)	3 / 3 (100.00%)
General disorders and administration site conditions
Facial oedema
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Oedema limbs
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Fever
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	2	0	1
Flu like symptoms
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
General disorders and administration site conditions - other, specify
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Pain
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	1 / 1 (100.00%)	0 / 3 (0.00%)
occurrences all number	2	3	1	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Confusion
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Psychiatric disorders - other, specify
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Restlessness
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	3	3	0	0
Alkaline phosphatase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Aspartate aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Blood bilirubin increased
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Investigations - other, specify
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Neutrophil count decreased
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	2	0	1
Platelet count decreased
subjects affected / exposed	1 / 3 (33.33%)	4 / 7 (57.14%)	0 / 1 (0.00%)	3 / 3 (100.00%)
occurrences all number	1	5	0	4
Weight gain
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
White blood cell decreased
subjects affected / exposed	2 / 3 (66.67%)	3 / 7 (42.86%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	3	4	0	1
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - other, specify
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Nervous system disorders
Lethargy
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Somnolence
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 3 (66.67%)	4 / 7 (57.14%)	1 / 1 (100.00%)	1 / 3 (33.33%)
occurrences all number	3	7	1	3
Blood and lymphatic system disorders - other, specify
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	2	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Constipation
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Diarrhoea
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Gastrointestinal disorders - other,specify
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	2	0	1
Mucositis oral
subjects affected / exposed	2 / 3 (66.67%)	2 / 7 (28.57%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	2	0	0
Nausea
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 1 (100.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	3 / 7 (42.86%)	1 / 1 (100.00%)	2 / 3 (66.67%)
occurrences all number	0	4	1	3
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Pruritus
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Rash maculo-papular
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Musculoskeletal and connective tissue disorders
Bone pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 1 (100.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Infections and infestations
Infections and infestations - other, specify
subjects affected / exposed	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 1 (0.00%)	2 / 3 (66.67%)
occurrences all number	0	2	0	2
Upper respiratory infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	1
Urinary tract infection
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Wound infection
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Hypoalbuminaemia
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	2	0	1
Hypocalcaemia
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	2	0	1
Hypokalaemia
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 1 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	2	0	1
Hypomagnesaemia
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Hypophosphataemia
subjects affected / exposed	2 / 3 (66.67%)	2 / 7 (28.57%)	0 / 1 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	4	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

03 Aug 2011

Reduction in the starting and escalated doses of AT9283, addition of skin biopsy and notification of a change to the Sponsor's contact details.

20 Jun 2012

Change to the AT9283 dose levels explored in the study (starting dose and escalated dose).

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.

Early termination of the trial due to poor recruitment, attributed to a lack of patients and new competing studies meant that only a small number of patients were administered AT9283 (across a total of three dose levels).

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Clinical trials

Clinical Trial Results:
A Cancer Research UK Phase I/IIa trial of AT9283 (a selective inhibitor of aurora kinases) given over 72 hours every 21 days via intravenous infusion in children and adolescents aged 6 months to 18 years with relapsed and refractory acute leukaemia.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Recommended Dose of AT9283 for Phase IIb Evaluation

Primary: Recommended Dose of AT9283 for Phase IIb Evaluation

Secondary: Safety

Secondary: Safety

Secondary: Response

Secondary: Response

Secondary: AT9283 Pharmacokinetic Profile

Secondary: AT9283 Pharmacokinetic Profile

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: A Cancer Research UK Phase I/IIa trial of AT9283 (a selective inhibitor of aurora kinases) given over 72 hours every 21 days via intravenous infusion in children and adolescents aged 6 months to 18 years with relapsed and refractory acute leukaemia.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Recommended Dose of AT9283 for Phase IIb Evaluation

Primary: Recommended Dose of AT9283 for Phase IIb Evaluation

Secondary: Safety

Secondary: Safety

Secondary: Response

Secondary: Response

Secondary: AT9283 Pharmacokinetic Profile

Secondary: AT9283 Pharmacokinetic Profile

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Cancer Research UK Phase I/IIa trial of AT9283 (a selective inhibitor of aurora kinases) given over 72 hours every 21 days via intravenous infusion in children and adolescents aged 6 months to 18 years with relapsed and refractory acute leukaemia.