E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The myelodysplastic syndrome (MDS) comprises a heterogenous group of hematopoietic stem cell disorders. - quantitative and morphologic abnormalities of bone marrow and peripheral blood cells - chromosomal abnormalities in about half of the cases: deletions , numerical aberrations and balanced translocations similar to those found in acute myeloid leukemia (AML). - DNA hypermethylation, mutations of ras genes, and loss of heterozygosity at tumor suppressor genes.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028536 |
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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 |
The main goal of this open-label randomized phase III trial is to assess the efficacy, toxicity, duration of hospitalization and quality of life of low dose Decitabine versus supportive care in elderly patients with a myelodysplastic syndrome.
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E.2.2 | Secondary objectives of the trial |
As part of the translational research: Unravel the cellular and molecular mechanisms by which the drug is active in MDS, with the long-term aim of improving treatment by defining rational drug combinations and schedules based upon a better understanding of the effect of Decitabine. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
♦ Patients aged 60 years and older with either: ♦ primary MDS without any pretreatment ♦ primary MDS pretreated with either growth factors, immunosuppressive agents or hydroxyurea. These drugs have to be stopped > 6 weeks before randomisation. ♦ secondary MDS (previous radio-/chemotherapy for solid tumors or lymphoma) and based on a BM aspiration or, in case of dry tap, on a BM biopsy, with either: ♦ Bone marrow blast count of 11-20%, ♦ Bone marrow blast count of ≤ 10% with poor cytogenetics: any numerical or structural abnormality of chromosome 7 and/or complex abnormalities (≥ 3 abnormalities) ♦ Bone marrow blast count of 21-30% (AML from MDS according to WHO proposal, RAEB-t according to FAB) in centers not participating in the AML elderly study of the EORTC. For these patients an observation period of one month is necessary to exclude those patients with a rapid progression towards full-blown AML.
NB: - The BM sample should be done within 3 weeks prior to randomization, the cytogenetics examination should be done within 8 weeks prior to randomization, the blood sample should be done within 1 week prior to randomization. - Patients for whom the cytogenetic examination was unsuccesful (this means that cytogenetic examination has been performed on BM or on blood material, but that the result was considered as a failure; ex: NN with < 10 mitoses), may be included in this trial, provided that the % of BM blasts is ≥5 % and/or 2-3 cytopenias are present. ♦ Absence of blast crisis of chronic myeloid leukemia. ♦ Absence of t(8;21), alone or in combination with other abnormalities ♦ Absence of pretreatment for MDS or AML with chemotherapy other than hydroxyurea. ♦ Absence of active malignancy in previous three years with the exception of basal or squamous cell skin cancer or cervical carcinoma in situ within two years of study registration. ♦ Ineligible for intensive chemotherapy (ex: an anthracycline and Ara-C) ♦ Performance status according to the WHO scale: 0, 1 or 2. ♦ Adequate renal and liver function: creatinine and bilirubin < 1.5 times the upper limit of normal. ♦ Absence of severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease, where New-York Heart Association (NYHA) Class III: marked limitation of activity; less than ordinary activity results in symptoms Class IV: unable to carry on any physical activity without discomfort; symptoms at rest. ♦ HIV negative and HBsAg negative. ♦ Absence of active uncontrolled infection. ♦ No prior history or current evidence of central nervous system and psychiatric disorders requiring hospitalization. ♦ Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. ♦ Before patient randomization, signed written informed consent must be given according to ICH GCP, and national/local regulations. N.B. Patients can be randomized only once in this trial. |
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E.4 | Principal exclusion criteria | |
E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | Information not present in EudraCT |
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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End of study occurs when all of the following criteria have been satisfied: 1. Thirty days after all patients have stopped protocol treatment 2. The trial is mature for the analysis of the primary endpoint as defined in the protocol 3. The database has been fully cleaned and frozen for this analysis |
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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 | 1 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |