Acute Myeloid Leukemia MedDRA version: 9.1 Level: LLT Classification code 10000880 Term: Acute myeloid leukaemia
Conditions
Interventions
Product Name: AZD1152 100mg Lyophile
Product Code: AZD1152
Pharmaceutical Form: Powder and solvent for solution for infusion
CAS Number: 722543-31-9
Current Sponsor code: AZD1152 Hydrate
Other descrip
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
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
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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). The outcome of Stage 1 will inform the decision as to whether the trial should continue to Stage 2. 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. ;Secondary Objective: Stage 1: AZD1152 monotherapy compared to LDAC 1. To assess the efficacy by assessment of Overall Survival (OS), Duration of Response (DoR), Disease-free Survival (DFS) and Time to Complete Response (TTCR). 2. To assess the effects on a) patients’ health related quality of life (HRQoL) and disease-related symptoms b) the number of key healthcare cost-generating events c) the requirement for key healthcare interventions 3. Safety/tolerability Stage 2: AZD1152, alone and in combination with LDAC, compared to LDAC alone 1. To determine the efficacy by assessment of OS, DoR, DFS and TTCR 2. To assess the effects on a) HRQoL and disease-related symptoms b) the number of key healthcare cost-generating events c) the requirement for key healthcare interventions 3. Safety/tolerability Stage 1 and 2: To determine the population PK of AZD1152 and AZD1152 hQPA, and to assess the relationship between PK and measures of PD response, efficacy and AEs in patients with AML;Primary end point(s): Overall Complete Response Rate (OCRR), defined as the proportion of patients achieving a Complete Remission (CR) or confirmed CRi (complete remission with incomplete recovery of neutrophils or platelets sustained at 2 consecutive assessments) | — |
Countries
France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed