CMMl 201

Trial overview

A phase 2 study of azacitidine in chronic myelomonocytic leukaemia (CMML)

Inclusion criteria

Patients with newly diagnosed or previously treated CMML-1 or CMML-2 according to WHO criteria (2008 (Appendix 3 of protocol)) 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:
- Red cell transfusion dependence and pre-transfusion Hb <9.0
- Symptomatic anaemia (Hb <11.5g/dl)
- Thrombocytopenia <50 x 109/l
- Symptomatic bleeding due to platelet functional defect or DIC/fibrinolysis
- WCC > 50 x 109/l
AND/OR
- Düsseldorf Score intermediate or high (Appendix 4 of protocol) for proliferative CMML-1 (i.e. WCC > 12 x 109/L)
- IPSS Score of Int-2 or High Risk (Appendix 5 or protocol) 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 at study entry (Appendix 6 of protocol).
6. Women of childbearing potential (WCBP) (Appendix 7 of protocol) 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 (Appendix 1 of protocol) 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 (Appendix 1 of protocol) throughout the study and for 3 months following the date of the last dose of study drug

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.
4. Pregnant or lactating females.
5. Use of any other experimental drug or therapy within 28 days of baseline.
6. Known hypersensitivity to azacitidine.
7. Known hypersensitivity to mannitol.
8. Other active malignant disease.
9. Known positive for HIV or infectious hepatitis, type B or C.
10. Active infection.