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)

February 21, 2020 updated by: AstraZeneca

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AZD1152 1200 mg
AZD1152 1200 mg, iv, 7 day infusion monotherapy
Drug: AZD1152
1200 mg, iv, 7 day infusion
Active Comparator: LDAC 20 mg
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
Drug: LDAC
20 mg, sc, bd, 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients With Overall Complete Response for Stage I
Time Frame: IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DoR): Stage I and Transition Phase
Time Frame: DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
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)
Disease Free Survival (DFS)
Time Frame: DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
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)
Time To Complete Response (TTCR)
Time Frame: Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
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)
Overall Survival (OS)
Time Frame: Assessed from randomisation until the date of death from any cause, assessed up to 24 months
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
Percent of Patients With Worsened Trial Outcome Index (TOI)
Time Frame: TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
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)
Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score.
Time Frame: FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Study Director: Paul Stockman, AstraZeneca
  • Principal Investigator: Hagop Kantarjian, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

August 4, 2009

First Submitted That Met QC Criteria

August 4, 2009

First Posted (Estimate)

August 6, 2009

Study Record Updates

Last Update Posted (Actual)

February 24, 2020

Last Update Submitted That Met QC Criteria

February 21, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D1531C00009

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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