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

Phase 2

Completed

Conditions: Acute Myeloid Leukemia

Interventions: Drug: LDAC
Drug: AZD1152

Registration Number: NCT00952588

Lead Sponsor: AstraZeneca

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 74

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LDAC 20 mg	LDAC	LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
AZD1152 1200 mg	AZD1152	AZD1152 1200 mg, iv, 7 day infusion monotherapy

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With Overall Complete Response for Stage I	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.

Secondary Outcome Measures

Name	Time	Method
Disease Free Survival (DFS)	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.
Duration of Response (DoR): Stage I and Transition Phase	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.
Time To Complete Response (TTCR)	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)
Overall Survival (OS)	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.
Percent of Patients With Worsened Trial Outcome Index (TOI)	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.
Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score.	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.