E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myelodysplastic syndromes |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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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 |
For the Phase I study : Determine the safety and tolerance of escalating doses of Idarubicine combined to Azacitidine in patients with INT-2 or Highr risk MDS.
For the phase II study: Primary: Evaluate rate and duration of response (according to IWG 2006 criteria and IWG 2000 criteria) to the combination of Idarubicine and Azacytidine in patients with INT-2 or Highr risk MDS.
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E.2.2 | Secondary objectives of the trial |
Secondary: - the safety (particularly hematological toxicity) of the combination - duration of response, - progression to AML, - survival. - the rate of hematological improvement
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Documented diagnosis of MDS, or CMML with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease, -IPSS score ≥1.5 -Myocardial function does not indicate cons the use of idarubicin -no contra indication to anthracyclines -Age ≥ 18 years -Perfornance Status ≤2 according to ECOG. -Serum creatinine < 1.5 x ULN and normal levels of electrolytes (serum sodium 136-145 nmmol/l, Potassium 3,5-4,5 mmol/l, alkaline Reserve 23-29 mmol/l, , Calcium 2,15-2,5 mmol/l, Phospohore 0,87-1,45 mmol/l) -Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) < 1.5 x upper limit of normal (ULN) -Serum total bilirubin < 1.5 x ULN. -Non eligible for an allogeneic stem cell transplantation. -Must be able to adhere to the study visit schedule and other protocol requirements -Signed informed consent. Female subjects of childbearing potential† must: • Accept effective contraception without interruption throughout the duration of study and up to three months after the end of treatment.
Male subjects must •Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy and up to three months after the final treatment if their partner is of childbearing potential and has no contraception.
•Agree to learn the procedures for preservation of sperm
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E.4 | Principal exclusion criteria |
Uncontrolled infection -Prior therapy with anthracycline for MDS. -Prior therapy with demethylating agents within the last 3 months -Prior therapy with Hematopoietic growth factor (ESA or G-CSF) agents or cytotoxic agents (oral chemotherapy, low doses AraC) within the last 30 days. -Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) -Pregnant or lactating females -Known HIV-1 positivity -Contra-indication to Anthracyclines
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E.5 End points |
E.5.1 | Primary end point(s) |
For Phase I: tolerance of two dose levels of idarubicin associated with azacitidine. It will be analyzed after 2 cycles,
For Phase II: number of complete responses (CR) + partial response (PR) + RC marrow by IWG 2006 criteria after 3 and 6 cycles of treatment.
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
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 | Yes |
E.7.1.3.1 | Other trial type description |
will assess the safety and tolerance of escalating doses of Idarubicine combined to Azacytidine |
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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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 17 |
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 | 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 | 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 | |
E.8.9.2 | In all countries concerned by the trial years | 2 |