E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Low and intermediate-1 risk MDS, and low-risk CMML. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009018 |
E.1.2 | Term | Chronic myelomonocytic leukaemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
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 |
•To assess the clinical efficacy, in terms of transfusion independence, of 6 cycles (24 weeks) of azacitidine given in transfusion-dependent patients with MDS and IPSS score low, intermediate-1 or low-risk CMML who are either refractory to or not eligible for treatment with erythropoietin +/- G-CSF (predictive group “poor” according to the predictive model)
•To assess effect of treatment on haemoglobin level |
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E.2.2 | Secondary objectives of the trial |
To assess the following; •Effect of treatment on white blood cells (WBC) and platelet (Plt) counts •Effect of treatment on marrow morphology and cytogenetics •Effect of treatment on genetic and epigenetic profiling of marrow cells •Effect of treatment with erythropoietin in patients not receiving TI at week 28 •Follow-up regarding survival and AML transformation until death
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must satisfy the following criteria to be enrolled in the study: • Must be >=18 years of age at the time of signing the informed consent form • MDS at IPSS Low or Int-1, or mixed MDS/MPD; either CMML with < 10% marrow blasts or RARS-T • Patients with high or intermediate probability for response according to the predictive model2 should be refractory to EPO / darbepoetin (equivalent to > 60 000 U of EPO / week for > 8 weeks) followed by EPO + G-CSF for > 8 weeks, or biosimilar drugs in equipotent doses, or EPO + G-CSF upfront for 8 weeks. Patients with low probability for response according to the predictive model, could be included without prior EPO/G-CSF treatment • Transfusion need >4 units over the last 8 weeks, or >8 units over the last 26 weeks. • Subject has signed the informed consent document. • Men and women of childbearing potential must use effective contraception during, and for up to 3 months after treatment.
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E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study: • Pregnant or lactating females. • Patients who are eligible for curative treatment • Expected survival less than 24 weeks. • Symptomatic thrombocytopenia / active bleeding • Patients with JAK-2 positive RARS-T if eligible for new investigational drugs • Serum biochemical values as follows 1. Serum creatinine >2.0 mg/dL (177 micromol/L) 2. Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN) 3. Serum total bilirubin >1.5 mg/dL (26 micromol/L) • Uncontrolled systemic infection • Considered not capable of following the study protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
•Effect of treatment on haemoglobin level at week 28 •Number of patients reaching transfusion-independency, TI, at week 28, defined as no transfusion needed during week 20-27
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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 | No |
E.6.4 | Safety | No |
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 | 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) | No |
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) | 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 | Information not present in EudraCT |
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) | 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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |