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To test the safety and activity of 5-aza-2′-deoxycytidine (decitabine) in patients with relapsed/refractory acute lymphocytic leukaemia ( ALL), we conducted a phase 1 study with two parts: administering decitabine alone or in combination with Hyper- CVAD (fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine). Patients participated in either part of the study or in both parts sequentially. In the initial part, decitabine was administered intravenously at doses of 10-120 mg/m2 per d for 5 d every other week in cycles of 28 d. In the combination part, patients were treated on the first 5 d of Hyper- CVAD with intravenous decitabine at 5-60 mg/m2 per d. A total of 39 patients received treatment in the study: 14 in the first part only, 16 sequentially in both parts and 9 in the second part only. Decitabine was tolerated at all doses administered, and grade 3 or 4 toxic effects included non-life-threatening hepatotoxicity and hyperglycaemia. Induction of DNA hypomethylation was observed at doses of decitabine up to 80 mg/m2. Some patients who had previously progressed on Hyper- CVAD alone achieved a complete response when decitabine was added. Decitabine alone or given with Hyper- CVAD is safe and has clinical activity in patients with advanced ALL. [ABSTRACT FROM AUTHOR]