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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00952588




Registration number
NCT00952588
Ethics application status
Date submitted
4/08/2009
Date registered
4/08/2009
Date last updated
13/02/2014

Titles & IDs
Public title
Study to Investigate the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC)in Acute Myeloid Leukaemia (AML) Patients
Scientific title
A Randomised, Open-label, Multi-centre, 2-stage, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC) in Comparison With LDAC Alone in Patients Aged = 60 With Newly Diagnosed Acute Myeloid Leukaemia (AML)
Secondary ID [1] 0 0
D1531C00009
Universal Trial Number (UTN)
Trial acronym
SPARK-AML1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD1152
Treatment: Drugs - LDAC

Experimental: AZD1152 1200 mg - AZD1152 1200 mg, iv, 7 day infusion monotherapy

Active Comparator: LDAC 20 mg - LDAC 20 mg, sc, bd, 10 days (400mg per cycle)


Treatment: Drugs: AZD1152
1200 mg, iv, 7 day infusion

Treatment: Drugs: LDAC
20 mg, sc, bd, 10 days

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Patients With Overall Complete Response for Stage I - Percentage of patients achieving either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi). Per Cheson Criteria: Confirmed complete remission (CRi) is defined as a disappearance of blasts in the peripheral blood; a decrease in bone marrow blasts to <5% total bone marrow nucleated cells demonstrated in bone marrow aspirate; absence of Auer rods; no persistent extramedullary leukaemia. Complete response (CR) is defined as all requirements to meet CRi and in addition: recovery of neutrophils to =1.0 x 109/L and platelets to =100 x 109/L; transfusion-independence.
Timepoint [1] 0 0
IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary outcome [1] 0 0
Duration of Response (DoR): Stage I and Transition Phase - DoR was defined for the median of days which showed a confirmed CRi or CR, as the time from first documented evidence of CRi or CR until the first documented sign of disease progression or death. Duration of Response was measured from the Response Start date until evidence of patient relapse or death. Stage I : 45 patients randomized in a 2:1 ratio to AZD1152 or LDAC. Transition phase: enrollment of up to 30 additional patients randomized as per stage I.
Timepoint [1] 0 0
DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary outcome [2] 0 0
Disease Free Survival (DFS) - Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.
Timepoint [2] 0 0
DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary outcome [3] 0 0
Time To Complete Response (TTCR) - TTCR is measured as time from randomization to either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi)
Timepoint [3] 0 0
Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary outcome [4] 0 0
Overall Survival (OS) - Overall Survival is defined as the median time from randomisation to death from any cause. Patients who were not known to have died at the time of the analysis were censored at the date they were last known to be alive.
Timepoint [4] 0 0
Assessed from randomisation until the date of death from any cause, assessed up to 24 months
Secondary outcome [5] 0 0
Percent of Patients With Worsened Trial Outcome Index (TOI) - TOI is derived from the sum of the Functional Well Being (FWB), Physical Well Being (PWB) and additional subscales of the FACT-Leu. The TOI subscale consists of 31 items with TOI scores ranging from 0 to 124. The TOI is described as a summary measure of HRQoL. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -9.
Timepoint [5] 0 0
TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary outcome [6] 0 0
Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score. - The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -11.
Timepoint [6] 0 0
FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)

Eligibility
Key inclusion criteria
- Provision of written informed consent

- Newly diagnosed male or female patients aged 60 and over

- De Novo or Secondary AML

- Not eligible for intensive induction with anthracycline-based combination chemotherapy
as a result of at least one of the following:Age =75 years; Adverse cytogenetics,
e.g., as defined by the MRC Prognostic Groupings; WHO performance status >2; Organ
dysfunction arising from significant co-morbidities not directly linked to leukaemia
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participation in another clinical study in which an investigational product was
received within 14 days before the first dose in this study, or at any time if the
patient has not recovered from side-effects associated with that investigational
product

- Administration of LDAC is clinically contraindicated

- Patients with AML of FAB M3 classification Acute Promyelocytic Leukaemia (APL)

- Patients with blast crisis of chronic myeloid leukaemia

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Westmead
Recruitment hospital [2] 0 0
Research Site - Herston
Recruitment hospital [3] 0 0
Research Site - Melbourne
Recruitment hospital [4] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
France
State/province [9] 0 0
Angers Cedex 01
Country [10] 0 0
France
State/province [10] 0 0
Clermont-ferrand
Country [11] 0 0
France
State/province [11] 0 0
Grenoble Cedex 09
Country [12] 0 0
France
State/province [12] 0 0
Lyon Cedex 03
Country [13] 0 0
France
State/province [13] 0 0
Marseille Cedex 09
Country [14] 0 0
France
State/province [14] 0 0
Nantes
Country [15] 0 0
Germany
State/province [15] 0 0
Duisburg
Country [16] 0 0
Germany
State/province [16] 0 0
Erlangen
Country [17] 0 0
Germany
State/province [17] 0 0
Frankfurt
Country [18] 0 0
Germany
State/province [18] 0 0
Munster
Country [19] 0 0
Germany
State/province [19] 0 0
Villingen-schwenningen
Country [20] 0 0
Italy
State/province [20] 0 0
BO
Country [21] 0 0
Italy
State/province [21] 0 0
GE
Country [22] 0 0
Italy
State/province [22] 0 0
TO
Country [23] 0 0
Italy
State/province [23] 0 0
UD
Country [24] 0 0
Italy
State/province [24] 0 0
Roma
Country [25] 0 0
Japan
State/province [25] 0 0
Aichi
Country [26] 0 0
Japan
State/province [26] 0 0
Fukui
Country [27] 0 0
Japan
State/province [27] 0 0
Gunma
Country [28] 0 0
Japan
State/province [28] 0 0
Kanagawa
Country [29] 0 0
Japan
State/province [29] 0 0
Tokyo
Country [30] 0 0
Japan
State/province [30] 0 0
Fukuoka
Country [31] 0 0
Romania
State/province [31] 0 0
Brasov
Country [32] 0 0
Romania
State/province [32] 0 0
Tg Mures
Country [33] 0 0
Spain
State/province [33] 0 0
Asturias
Country [34] 0 0
Spain
State/province [34] 0 0
Cataluna
Country [35] 0 0
Spain
State/province [35] 0 0
Comunidad de Madrid
Country [36] 0 0
Spain
State/province [36] 0 0
Comunidad Valenciana
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Brighton
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the efficacy, safety and tolerability of AZD1152 alone
and in combination with low dose cytosine arabinoside (LDAC) in comparison with LDAC alone in
AML patients.
Trial website
https://clinicaltrials.gov/show/NCT00952588
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul Stockman
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications