Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia in Accelerated and Blastic Phase

Inclusion criteria

• Male or female patients * 18 years of age
• Accelerated phase of CML defined as the presence of one or more of the following:

• percentage of blasts in blood or bone marrow * 15% but < 30%
• percentage of blasts plus promyelocytes in the peripheral blood or bone marrow * 30% (providing that < 30% blasts are present in the bone marrow)
• peripheral basophils * 20%
• thrombocytopenia < 100 x 109/L unrelated to therapy These criteria must be met within 4 weeks of administration of first dose of trial treatment.
• Blastic phase of CML defined as the presence of one or more of the following:

• percentage of blasts in blood or bone marrow * 30%
• percentage of blasts and promyelocytes in blood or bone marrow * 50%
• documented extramedullary blast involvement (skin, lymph node, bone, lung).
• Voluntary written informed consent.

Exclusion criteria

• Patients of childbearing potential wihout a negative pregnancy test prior to the initiation of study drug. Barrier contraceptive precautions are to be used throughout the trial in both sexes.
• Patients with an ECOG Performance Status Score ** 3 (see Section 7.2.1)
• Creatinine levels more than 2 x's the ULN at the laboratory where the analysis was performed.
• Total serum bilirubin more than 1.5 x's the upper limit of the normal range (ULN) at the laboratory where the analyses were performed; in patients with clinically suspected leukemic involvement of the liver, total bilirubin more than 3 x's the ULN
• AST (SGOT) or ALT (SGPT) more than 3 x's the upper limit of the normal range (ULN) at the laboratory where the analyses were performed; in patients with clinically suspected leukemic involvement of the liver, AST and ALT more than 5 x's the ULN
• Patients receiving treatment with interferon-alpha within 48 hours of Day 1.
• Patients receiving treatment with hydroxyurea within 24 hours of Day 1
• Patients receiving treatment with homoharringtonine within 14 days of Day 1
• Patients receiving treatment with low-dose cytosine arabinoside (< 30 mg/m2 every 12 to 24 hours administered daily) within seven days of Day 1
• Patients receiving treatment with moderate dose cytosine arabinoside (100-200 mg/m2 for 5 to 6 days) within 14 days of Day 1.
• Patients receiving treatment with high-dose cytosine arabinoside (1-3 g(m2 every 12 to 24 hours for six to 12 doses) within 28 days of Day 1.
• Patients receiving anthracyclines, mitoxantrone, etoposide, methotrexate or cyclophosphamide within 21 days of Day1.
• Patients receiving busulfan within six weeks of Day 1.
• Patients receiving anti-leukemic agents not included in Exclusion Criteria 6-13 should not begin treatment with STI571 until sufficient time has elapsed for potential recovery to have occurred in the nadir in blood counts. In practice, a full recovery of blood counts may not be possible due to progression of the underlying disease.
• Patients receiving any hematopoietic stem cell transplantation and who have not achieved full hematopoietic recovery following the transplant
• Patients receiving any other investigational agents within 28 days of Day 1.
• Patients with Grade ¾ cardiac disease.
• Patients with any serious concomitant medical condition
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.
• Patients with a prior diagnosis of accelerated or blastic phase who are in remission and do not fit inclusion criteria, are not eligible.
• Patients who are likely to be submitted to any procedure of stem cell transplantation before the end of the treatment (6 months), are not eligible.