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

Acute Myeloid Leukemia Clinical Trial

— SPARK-AML1  

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00952588
• Other study ID #: D1531C00009
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2009
• Est. completion date: June 2011

Study information

• Verified date: February 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• AZD1152
1200 mg, iv, 7 day infusion
• LDAC
20 mg, sc, bd, 10 days

Locations

Country	Name	City	State
Australia	Research Site	Herston	Queensland
Australia	Research Site	Melbourne	Victoria
Australia	Research Site	Parkville	Victoria
Australia	Research Site	Westmead	New South Wales
France	Research Site	Angers Cedex 01
France	Research Site	Clermont-ferrand
France	Research Site	Grenoble Cedex 09
France	Research Site	Lyon Cedex 03
France	Research Site	Marseille Cedex 09
France	Research Site	Nantes
Germany	Research Site	Duisburg
Germany	Research Site	Erlangen
Germany	Research Site	Frankfurt
Germany	Research Site	Munster
Germany	Research Site	Villingen-schwenningen
Italy	Research Site	Bologna	BO
Italy	Research Site	Genova	GE
Italy	Research Site	Orbassano	TO
Italy	Research Site	Roma
Italy	Research Site	Udine	UD
Japan	Research Site	Chuo	Tokyo
Japan	Research Site	Fukuoka
Japan	Research Site	Isehara	Kanagawa
Japan	Research Site	Maebashi	Gunma
Japan	Research Site	Nagoya	Aichi
Japan	Research Site	Yokohama	Kanagawa
Japan	Research Site	Yoshida-gun	Fukui
Romania	Research Site	Brasov
Romania	Research Site	TG Mures
Spain	Research Site	Badalona(barcelona)	Cataluna
Spain	Research Site	Barcelona	Cataluna
Spain	Research Site	Madrid	Comunidad DE Madrid
Spain	Research Site	Majadahonda	Madrid
Spain	Research Site	Oviedo	Asturias
Spain	Research Site	Valencia	Comunidad Valenciana
United Kingdom	Research Site	Brighton
United Kingdom	Research Site	London
United States	Research Site	Atlanta	Georgia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Greenville	South Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Italy,  Japan,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary	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.	DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary	Disease Free Survival (DFS)	Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.	DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary	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)	Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary	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.	Assessed from randomisation until the date of death from any cause, assessed up to 24 months
Secondary	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.	TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary	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.	FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)