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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 (SPARK-AML1)

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD1152
LDAC
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukaemia,, AML

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

AZD1152 1200 mg

LDAC 20 mg

Arm Description

AZD1152 1200 mg, iv, 7 day infusion monotherapy

LDAC 20 mg, sc, bd, 10 days (400mg per cycle)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Disease Free Survival (DFS)
Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.
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)
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.
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.
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.

Full Information

First Posted
August 4, 2009
Last Updated
February 21, 2020
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00952588
Brief 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
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Acute Myeloid Leukaemia,, AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AZD1152 1200 mg
Arm Type
Experimental
Arm Description
AZD1152 1200 mg, iv, 7 day infusion monotherapy
Arm Title
LDAC 20 mg
Arm Type
Active Comparator
Arm Description
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
Intervention Type
Drug
Intervention Name(s)
AZD1152
Intervention Description
1200 mg, iv, 7 day infusion
Intervention Type
Drug
Intervention Name(s)
LDAC
Intervention Description
20 mg, sc, bd, 10 days
Primary Outcome Measure Information:
Title
Percentage of Patients With Overall Complete Response for Stage I
Description
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.
Time Frame
IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary Outcome Measure Information:
Title
Duration of Response (DoR): Stage I and Transition Phase
Description
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.
Time Frame
DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Title
Disease Free Survival (DFS)
Description
Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.
Time Frame
DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Title
Time To Complete Response (TTCR)
Description
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)
Time Frame
Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Title
Overall Survival (OS)
Description
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.
Time Frame
Assessed from randomisation until the date of death from any cause, assessed up to 24 months
Title
Percent of Patients With Worsened Trial Outcome Index (TOI)
Description
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.
Time Frame
TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Title
Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score.
Description
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.
Time Frame
FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Stockman
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Hagop Kantarjian
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Westmead
State/Province
New South Wales
Country
Australia
Facility Name
Research Site
City
Herston
State/Province
Queensland
Country
Australia
Facility Name
Research Site
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Research Site
City
Parkville
State/Province
Victoria
Country
Australia
Facility Name
Research Site
City
Angers Cedex 01
Country
France
Facility Name
Research Site
City
Clermont-ferrand
Country
France
Facility Name
Research Site
City
Grenoble Cedex 09
Country
France
Facility Name
Research Site
City
Lyon Cedex 03
Country
France
Facility Name
Research Site
City
Marseille Cedex 09
Country
France
Facility Name
Research Site
City
Nantes
Country
France
Facility Name
Research Site
City
Duisburg
Country
Germany
Facility Name
Research Site
City
Erlangen
Country
Germany
Facility Name
Research Site
City
Frankfurt
Country
Germany
Facility Name
Research Site
City
Munster
Country
Germany
Facility Name
Research Site
City
Villingen-schwenningen
Country
Germany
Facility Name
Research Site
City
Bologna
State/Province
BO
Country
Italy
Facility Name
Research Site
City
Genova
State/Province
GE
Country
Italy
Facility Name
Research Site
City
Orbassano
State/Province
TO
Country
Italy
Facility Name
Research Site
City
Udine
State/Province
UD
Country
Italy
Facility Name
Research Site
City
Roma
Country
Italy
Facility Name
Research Site
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Research Site
City
Yoshida-gun
State/Province
Fukui
Country
Japan
Facility Name
Research Site
City
Maebashi
State/Province
Gunma
Country
Japan
Facility Name
Research Site
City
Isehara
State/Province
Kanagawa
Country
Japan
Facility Name
Research Site
City
Yokohama
State/Province
Kanagawa
Country
Japan
Facility Name
Research Site
City
Chuo
State/Province
Tokyo
Country
Japan
Facility Name
Research Site
City
Fukuoka
Country
Japan
Facility Name
Research Site
City
Brasov
Country
Romania
Facility Name
Research Site
City
TG Mures
Country
Romania
Facility Name
Research Site
City
Oviedo
State/Province
Asturias
Country
Spain
Facility Name
Research Site
City
Badalona(barcelona)
State/Province
Cataluna
Country
Spain
Facility Name
Research Site
City
Barcelona
State/Province
Cataluna
Country
Spain
Facility Name
Research Site
City
Madrid
State/Province
Comunidad DE Madrid
Country
Spain
Facility Name
Research Site
City
Valencia
State/Province
Comunidad Valenciana
Country
Spain
Facility Name
Research Site
City
Majadahonda
State/Province
Madrid
Country
Spain
Facility Name
Research Site
City
Brighton
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23071272
Citation
Quintas-Cardama A, Ravandi F, Liu-Dumlao T, Brandt M, Faderl S, Pierce S, Borthakur G, Garcia-Manero G, Cortes J, Kantarjian H. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood. 2012 Dec 6;120(24):4840-5. doi: 10.1182/blood-2012-06-436055. Epub 2012 Oct 15.
Results Reference
derived

Learn more about this trial

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

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