E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Myelomonocytic Leukaemia (CMML): Patients with newly diagnosed or previously treated CMML-1 or CMML-2. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009018 |
E.1.2 | Term | Chronic myelomonocytic leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 assess the safety, tolerability and efficacy of azacitidine in patients with CMML. |
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E.2.2 | Secondary objectives of the trial |
To assess response of disease to azacitidine, specifically:
• Incidence of CR/PR
• Haematological improvement
• Overall survival
• Progression-free survival
• Time to AML transformation of CMML
• Time to death or AML transformation of CMML
• Biological correlates |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with newly diagnosed or previously treated CMML-1 or CMML-2 according to WHO criteria (2008) with the following characteristics are eligibile for this study:
1. All CMML-2 patients are eligible.
2. For patients classified as CMML-1, the following must be present:
• Symptomatic bone marrow failure / myeloproliferation defined as any of the following:
o Red cell transfusion dependence and pre-transfusion Hb <9.0
o Symptomatic anaemia (Hb <11.5g/dl)
o Thrombocytopenia <50 x 109/l
o Symptomatic bleeding due to platelet functional defect or DIC/fibrinolysis
o WCC > 50 x 109/l
AND/OR
• Düsseldorf Score intermediate or high (Appendix 4) for proliferative CMML-1 (i.e. WCC > 12 x 109/L)
• IPSS Score of Int-2 or High Risk (Appendix 5) for non-proliferative CMML-1 (i.e. WCC <12 x 109/L)
AND/OR
• Systemic symptoms including weight loss with no alternative explanation (10% of baseline weight within previous 6 months)
• Symptomatic splenomegaly
• Symptomatic extramedullary involvement e.g. skin infiltration, serous effusions
3. Subject is able and willing to sign the Informed Consent Form.
4. Age 18 years or over at the time of signing the informed consent form.
5. WHO performance status of 2 or less than 2 at study entry.
6. Women of childbearing potential (WCBP) must have a negative urine pregnancy test within 7 days prior to start of study drug.
7. WCBP 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 drug.
8. Men whose partner is a WCBP must use at least 2 effective contraceptive methods throughout the study and for 3 months following the date of the last dose of study drug. |
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E.4 | Principal exclusion criteria |
1. CMML with eosinophilia and 5q33 abnormality.
2. Previous chemotherapy for CMML except Hydroxycarbamide.
3. Creatinine concentration > 2 x the institutional upper limit of the normal range within 28 days of registration.
4. Pregnant or lactating females.
5. Use of any other experimental drug or therapy within 28 days of registration.
6. Known hypersensitivity to azacitidine.
7. Known hypersensitivity to mannitol.
8. Other active malignant disease (including basal or squamous cell carcinoma of the skin).
9. Known positive for HIV or infectious hepatitis, type B or C.
10. Active infection. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• To assess the safety and tolerability of azacitidine
• To assess the overall response rate
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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) | 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 | No |
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 | 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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The end of the trial is defined as the date of the last participant’s last data item |
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |