E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The myelodysplastic syndromes (MDS) are a group of potentially acute myeloid leukemic disorders. The disorders of myeloid origin include acute myeloid leukemia (AML), MDS and myeloproliferative disorders such as chronic myeloid leukemia. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028533 |
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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 |
To determine the effect of azactidine plus Best Supportive Care, as compared with Conventional Care Regimens plus Best Supportive Care, on survival in MDS patients. |
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E.2.2 | Secondary objectives of the trial |
To determine the • effect of azacitidine plus Best Supportive Care (BSC), relative to Conventional Care Regimens (CCR) plus BSC, on hematologic status and episodes of infections requiring IV antibiotics ; • time to Relapse after complete remission (CR) or partial remission (PR), or Disease Progression , censored at death, in MDS patients treated with azacitidine plus BSC, compared to patients receiving CCR plus BSC; • time to transformation to AML, censored at death, in MDS patients treated with azacitidine plus BSC compared to patients receiving CCR plus BSC; • effect of azacitidine plus BSC, relative to that of CCR plus BSC on time to AML transformation or death from any cause; • safety and toxicity of azacitidine plus BSC, relative to CCR plus BSC in MDS patients; • to examine pharmacoeconomic differences in MDS patients treated with azacitidine plus BSC, compared to patients receiving CCR plus BSC. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Have an IPSS score of INT-2 or High and a diagnosis of RAEB or RAEBT per FAB classification criteria or a diagnosis of Myelodysplastic CMMoL per modified FAB criteria meeting the following: a. Monocytosis in peripheral blood >1x109/L, b. Dysplasia in one or more myeloid cell lines, c. 10 to 29% blasts in the BM d. WBC <13,000 X109/L ; 2. Be ≥18 years of age; 3. Have a life expectancy ≥3 months; 4. Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission; 5. Be capable of giving informed consent and have signed the informed consent form (ICF); 6. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status Grade of 0-2; 7. Have 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); 8. Have serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels ≤2 x ULN; 9. Have serum creatinine levels ≤1.5 x ULN; 10. Women of childbearing potential may participate, providing they meet the following conditions: a. Must agree to use at least 2 effective contraceptive methods throughout the study and for 3 months following the date of the last dose of study medication. b. Must have a negative serum pregnancy test obtained within 24 hours prior to Day 1. 11. Males with female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and should avoid fathering a child for 6 months following the date of the last dose of study medication. |
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E.4 | Principal exclusion criteria |
1. Secondary MDS, i.e., MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases; 2. Any prior treatment with azacitidine; 3. Any prior history of AML; 4. Any diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma with no complications); 5. Any diagnosis of metastatic disease; 6. Have hepatic tumors; 7. Radiation therapy, chemotherapy, or cytotoxic therapy, given to treat conditions other than MDS and administered within the previous 12 months prior to the first day of treatment (Day 1); 8. Known or suspected hypersensitivity to azacitidine or mannitol; 9. Prior or active disease that, in the opinion of the Investigator, may interfere with the procedures or evaluations to be conducted in the study; 10. Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS; 11. Serious medical illness likely to limit survival to ≤12 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); 12. Psychiatric illness that would prevent granting of informed consent; 13. Treatment with erythropoietin or myeloid growth factors (granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF]) during the previous 21 days prior to Day 1; 14. Treatment with androgenic hormones during the previous 14 days prior to Day 1; 15. Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C; 16. Treatment with other investigational drugs within the previous 30 days prior to Day 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period; 17. Within the 28-day screening period, documented red cell folate deficiency, as evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to death from any cause. |
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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 | 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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |