Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia Who Are Resistant to or Intolerant of *-Interferon. A Phase II Study
1. Male or female patients * 18 years of age.
2. Patients with Ph chromosome positive CML in the chronic-phase of the disease.
3. Patients must have documented resistance to an interferon-alpha containing therapy,
defined as any of the following:
1. Hematologic Resistance - Failure to achieve a complete hematologic response,
lasting for at least 1 month despite of 6 or more months of an interferon-alpha
2. Cytogenetic Resistance - Bone marrow cytogenetics showing *65% Ph chromosome
positivity after at least one year of interferon-alpha based therapy
3. Cytogenetic Refractoriness - An increase in the Ph+ chromosome bone marrow cells
by at least 30 percentage points (eg., from 20% to 50%, or from 30% to 60%)
confirmed by two samples at least 1 month apart, or an increase to * 65%
4. Hematologic Refractoriness - A rising WBC count (*100% increase and to a level
*20 x 109/L confirmed by two samples taken at least two weeks apart) while
receiving an interferon-alpha containing regimen.
4. Patients who have demonstrated intolerance to interferon-alpha therapy defined as: a
documented * Grade 3 non-hematologic toxicity (grade 2 in case of neurologic or
neuropsichiatric toxicity), persisting for more than 2 weeks, in a patient receiving
an interferon-alpha containing regimen. Patients who are intolerant to
interferon-alpha must be more than 3 months from time of diagnosis.
5. Written voluntary informed consent.
1. Patients of childbearing potential without a negative pregnancy test prior to the
initiation of study drug. Barrier contraceptive precautions are to be used
throughout the trial in both sexes.
2. Serum bilirubin and creatinine concentrations more than twice the upper limit of the
3. SGOT and SGPT more than twice the upper limit of the normal range.
4. Percentage of blasts, or basophils in the peripheral blood or bone marrow > 15%.
5. Percentage of blasts plus promyelocytes in the peripheral blood or bone marrow ( 30%.
6. Patients with a platelet count < 100 x 109/L
7. Patients with an ECOG Performance Status Score * 3.
8. Patients receiving busulfan within 6 weeks of Visit 1.
9. Patients receiving treatment with interferon-alpha within 14 days of Visit 1.
10. Patients receiving treatment with cytosine arabinoside within 14 days of Visit 1.
11. Patients receiving treatment with hydroxyurea within 7 days of Visit 1.
12. Patients who have received other investigational agents within 28 days of Visit 1.
13. Patients with Grade 3/4 cardiac problems as defined by the New York Heart Association
14. Patients with a history of non-compliance to medical regimens or who are considered
15. Patients who are likely to be submitted to any transplantation procedure during the
study period (12 months)