E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the overall survival in patients 65 years and older who have newly diagnosed de novo or secondary Acute Myloid Leukemia and either poor or intermediate risk cytogenetics who are randomly assigned to receive either decitabine or patients choice with physicians advice of either supportive care or low dose cytarabine. |
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E.2.2 | Secondary objectives of the trial |
To compare complete remission rates between treatment arms. To characterize and compare the incidence and severity of toxicities in the two treatment arms. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients may be included in the study only if they meet all of the following criteria:
1. Must sign an institutional review board/ethics committee-approved informed consent.
2. Must have a newly diagnosed, histologically confirmed de novo or secondary AML using the World Health Organization classification (e.g., ≥20% blasts).
3. Must be at least 65 years of age and have either poor- or intermediate-risk cytogenetics as categorized by Southwest Oncology Group.
4. Must have a performance status of 0-2 on the Eastern Cooperative Oncology Group scale (see protocol appendix 1)
5. Must have adequate organ function, defined as: - Hematology: WBC ≤ 40,000/mm; - Hepatic: Bilirubin less than or equal to 1.5 times the upper limit of normal, AST or ALT less than or equal 2.5 times the upper limit of normal; and - Renal: Creatinine clearance (calculated by the Cockroft and Gault method) greater than or equal to 50 mL/min;
6. Must have a life expectancy of at least 12 weeks.
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E.4 | Principal exclusion criteria |
1. Must not have acute promyelocytic leukemia (M3 classification).
2. Must not have t(8;21), inv(16) or t(15;17) karyotype abnormalities.
3. Must not have known CNS leukemia.
4. Must not have any other active systemic malignancies.
5. Must not have unstable angina or New York Heart Association (NYHA) class 3 or 4 congestive heart failure (see protocol appendix 3).
6. Must not have inaspirable bone marrow.
7. Must not have received previous chemotherapy (except hydroxyurea), including azacytidine (Vidaza), cytarabine or decitabine, for any myeloid disorder.
8. Must not have chronic respiratory disease that requires continuous oxygen use.
9. Must not have received any experimental drug within 4 weeks of randomization.
10. Must not be a candidate for a bone marrow or stem cell transplant within 12 weeks after randomization.
11. Must not have any concomitant medical or psychiatric disorders incompatible with the study (at the discretion of the investigator).
12. Must not have any comorbidity that causes organ dysfunction that is not related to leukemia.
13. Must not have an uncontrolled active infection(s) requiring IV antibiotics.
14. Must not have known HIV.
15. Must not have had radiotherapy for extramedullary disease within 2 weeks prior to study randomization.
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E.5 End points |
E.5.1 | Primary end point(s) |
Patients may remain on study treatment until one of the following occurs:
• death;
• for patients receiving decitabine or cytarabine, relapse or disease progression (see protocol section 3.5.5.);
• for patients receiving decitabine or cytarabine, no longer deriving clinical benefit from therapy;
• unacceptable toxicity;
• intercurrent illness that prevents further administration of treatment;
• patient/physician request; or,
• general or specific changes in the patient’s condition that renders the patient unacceptable for further treatment in the judgment of the investigator.
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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 | No |
E.6.5 | Efficacy | No |
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 | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | Yes |
E.8.2.3.1 | Comparator description |
Cytarabine or Pallative care |
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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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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The end of trial is defined as the last patient, last visit |
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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 | |
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 |