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) who are considered unsuitable to receive intensive induction chemotherapy regimens

Phase 1

Conditions: Acute Myeloid Leukemia
MedDRA version: 9.1 Level: LLT Classification code 10000880 Term: Acute myeloid leukaemia

Registration Number: EUCTR2009-010114-30-GB

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 420

Inclusion Criteria

1.Provision of written informed consent prior to any study specific procedures
2.Newly diagnosed male or female patients aged = 60 years
3.De Novo (primary) or Secondary AML
4.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 (Grimwade et al 2001)
- WHO performance status >2
- Organ dysfunction arising from significant co-morbidities not directly linked to leukaemia
5.World Health Organisation (WHO) performance status 0-3 (WHO performance status 3 is only acceptable if solely attributed to the underlying leukaemia)
6.Serum bilirubin = 1.5 x Upper Limit of Normal (ULN) unless considered due to leukaemic organ involvement (Gilbert’s or related syndrome allowed)
7.Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) = 2.5 x ULN, unless considered due to leukaemic organ involvement
8.Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance > 50 mL/min (measured or calculated by Cockcroft-Gault)
9.Likely ability to complete 3 cycles (12 weeks) of treatment
10.Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site and/or agents for AstraZeneca)
2.Previous randomisation of treatment in the present study
3.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 (to CTCAE Grade 1 or baseline, except alopecia)
4.Administration of LDAC is clinically contraindicated
5.Patients with AML of FAB M3 classification Acute Promyelocytic Leukaemia (APL)
6.Patients with blast crisis of chronic myeloid leukaemia
7.Mean QTc interval = 470ms calculated from 3 ECGs using Fridericia’s or Bazett’s Correction
8.Any chemotherapy e.g. for prior MDS, apart from hydroxyurea or intrathecal chemotherapy for CNS disease (see section 6.4), or radiotherapy within 14 days prior to starting the study (not including palliative radiotherapy at local sites)
9.Persistent, chronic, clinically significant toxicities, from any prior anti-cancer therapy greater than CTCAE Grade 1 (except alopecia)
10.Patients with symptomatic clinically defined central nervous system (CNS) disease due to leukaemic infiltration (asymptomatic patients are eligible if symptom free for > 10 days)
11.Uncontrolled intercurrent illness including, but not limited to active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations which would limit compliance with protocol requirements
12.Major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that involved general anaesthesia or respiratory assistance
13.Patients with documented cases of human immunodeficiency virus (HIV) or hepatitis B or C
14.Female patients who are breast feeding, or patients of reproductive potential not employing an effective method of birth control
15.History of hypersensitivity to active or inactive excipients of any study medication (AZD1152 or LDAC)
16. Lack of capacity to give adequate informed consent as assessed by the patient’s AML care physician

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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