E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukaemia (AML) de novo or secondary AML to myelodysplastic syndrome (MDS)/chemotherapy/radiotherapy. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Stage 1. The primary objective of Stage 1 is to make a preliminary assessment of the relative efficacy of AZD1152 monotherapy compared to low dose cytosine arabinoside (cytarabine, LDAC) by assessment of Overall Complete Response Rate (OCRR). Stage 2. The primary objective of Stage 2 is to determine the relative efficacy of AZD1152, both alone, and in combination with LDAC compared to LDAC alone by assessment of OCRR. |
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E.2.2 | Secondary objectives of the trial |
Stage 1. 1.To assess the efficacy of AZD1152 monotherapy compared to LDAC by assessment of Overall Survival (OS), Duration of Response (DoR) and Time to Complete Response (TTCR). 2.To assess the effects of AZD1152 monotherapy compared to LDAC on patients health related quality of life (HRQoL) and disease-related symptoms. 3.To assess the effects of AZD1152 monotherapy compared to LDAC on the number of key healthcare cost-generating events. 4.To assess the effects of AZD1152 monotherapy compared to LDAC on the requirement for key healthcare interventions. 5.To assess the safety and tolerability of AZD1152 monotherapy compared with LDAC. Stage 2 1.To determine the efficacy of AZD1152, alone and in combination with LDAC, compared to LDAC alone, by assessment of Overall Survival (OS), Duration of Response (DoR) and Time to Complete Response (TTCR). 2.To assess the effects of AZD1152, alone and in combination with LDAC, compared to LDAC alone, by assessment of patients health re |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 chemotherapy because of medical, social or psychological reasons 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 (Gilberts 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. |
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E.4 | Principal 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 Fridericias or Bazetts Correction 8. Any chemotherapy e.g. for prior MDS, 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 (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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy OCRR, defined as the proportion of patients achieving either a complete remission (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (CRi) (see section 12.2). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |