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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00952588
First received: August 4, 2009
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: AZD1152
Drug: LDAC
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011) ] [ Designated as safety issue: No ]
    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) [ Time Frame: DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011) ] [ Designated as safety issue: No ]
    Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.

  • Time To Complete Response (TTCR) [ Time Frame: Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Assessed from randomisation until the date of death from any cause, assessed up to 24 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011) ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011) ] [ Designated as safety issue: No ]
    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.


Enrollment: 74
Study Start Date: July 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00952588

  Show 45 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Paul Stockman AstraZeneca
Principal Investigator: Hagop Kantarjian M.D. Anderson Cancer Center
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00952588     History of Changes
Other Study ID Numbers: D1531C00009
Study First Received: August 4, 2009
Results First Received: February 1, 2013
Last Updated: February 13, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Italy: The Italian Medicines Agency
Spain: Comité Ético de Investigación Clínica
Spain: Spanish Agency of Medicines
Australia: Department of Health and Ageing Therapeutic Goods Administration
Japan: Ministry of Health, Labor and Welfare
Romania: National Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Acute Myeloid Leukaemia,
AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014