E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with acute myeloid leukemia not eligible for or resistant to chemotherapy |
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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 |
Primary Objective • determine the safety of azacitidine administration in AML patients.
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives - determine the response rate in patients with AML treated with azacitidine including: - incidence of CR and PR - incidence of hematologic improvement (HI) and stable disease (SD) in patients not achieving CR or PR - determine the time to relapse after CR, PR, HI, and SD or Disease Progression (according to IWG criteria) in AML patients treated with azacitidine - determine overall survival - Health resources utilization, including: - Duration of hospitalization for any reason - Number of infections requiring intravenous antibiotic treatment (antibacterial or antifungal) - Blood product transfusion - Molecular and methylation analysis to identify certain prognostic factors that may predict response to azacitidine.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 20 patients with: a) newly diagnosed de novo or secondary AMLs not eligible for induction chemotherapy 2. 20 patients with a) chemotherapy refractory AML (all age groups) b) relapsed AML (all patients over the age of 60 years or those ineligible for chemotherapy) These patients are entered if the meet the following inclusion criteria: 1. ≥18 years of age; 2. life expectancy ≥1 months; 3. Be capable of giving informed consent and have signed the informed consent form (ICF); 4. serum bilirubin levels ≤1.5 x the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis (as indicated by positive direct Coombs’ testing, decreased haptoglobin level, elevated indirect bilirubin and/or lactate dehydrogenase [LDH]), or ineffective erythropoiesis (as indicated by bone marrow findings); 5. serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels ≤2 x ULN; 6. serum creatinine levels ≤1.5 x ULN; 7. Women of childbearing potential may participate, providing they meet the following conditions: -Must agree to use effective contraceptive methods throughout the study and for 3 months following the date of the last dose of study medication. -Must have a negative serum pregnancy test obtained within 24 hours prior to Day 1. 8. Males with female partner of childbearing potential must agree to use effective contraceptive methods throughout the study and should avoid fathering a child for 3 months following the date of the last dose of study medication.
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E.4 | Principal exclusion criteria |
Patients meeting any of the following criteria will not be included in the study:
1. Any diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma with no complications); 2. Any diagnosis of metastatic disease; 3. hepatic tumors; 4. Known or suspected hypersensitivity to azacitidine or mannitol; 5. Prior or active disease that, in the opinion of the Investigator, may interfere with the procedures or evaluations to be conducted in the study; 6. Serious medical illness likely to limit survival to ≤1 months after screening or likely to prevent granting of informed consent (e.g., history of severe congestive heart failure, clinically unstable cardiac disease, or pulmonary disease); 7. Psychiatric illness that would prevent granting of informed consent; 8. Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C; 9. Treatment with other investigational drugs, including thalidomide and arsenic trioxide, within the previous 30 days prior to Day 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period.
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E.5 End points |
E.5.1 | Primary end point(s) |
For the primary safety variable, the incidence of AEs, and SAE, descriptive statistics will be used. Univariable analysis using the log-rank tests will be used to analyze AEs, and SAE according to patient- and disease variables. Multivariable analysis by using Cox regression models will be performed to analyze AEs, and SAE according to patient- and disease variables.
Secondary Efficacy Variables For the secondary efficacy variable, response to azacitidine, descriptive statistics will be used. Univariable analysis using the log-rank tests will be used to analyze response, time-to-event secondary efficacy variables, and time to death from any cause according to patient- and disease variables. Multivariable analysis by using Cox regression models will be performed to analyze response to azacitidine, time-to-event secondary efficacy variables, and time to death from any cause according to patient- and disease variables. will be analyzed The number of infections requiring treatment with intravenous antibiotics (antibacterial or antifungal), the number of required transfusions of blood products, the number of days spent in hospital and the peripheral counts will be analyzed using descriptive statistics.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
scientific analysis (ex. methylation of cells...etc.) |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |