Randomized Study Comparing the Effect of Dasatinib and Imatinib on Malignant Stem Cells in Chronic Myeloid Leukemia (NordCML006)

Inclusion Criteria:

• Patients are able to provide written informed consent

• Patients must have CML in CP which is defined by the presence of all of the following criteria:

  • < 15% blasts in peripheral blood (PB) and BM.
  • < 30% blasts plus promyelocytes in PB and BM.
  • < 20% basophils in the PB.
  • ≥ 100 x 109/L platelets.
  • No evidence of extramedullary leukemia apart from hepatosplenomegaly
  • Ph+ or variants must be demonstrated by BM cytogenetics, FISH or PCR.
  • Previously untreated CML in CP, with the exception of hydroxyurea or anagrelide
• Patients must be enrolled in this study within 90 days after the date of first being diagnosed with CML
• ECOG Performance Status (PS) Score 0 - 1 (see Appendix 2)
• Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional upper limit of normal (ULN) in absence of Gilbert type unconjugated hyperbilirubinemia; alanine aminotransferase (ALAT≤ 2.5 times the institutional ULN.
• Adequate renal function defined as serum creatinine ≤ 2 times the institutional ULN.
• Men and women, ages 18 years and older.
• Adequate BM aspiration sample before the start of study treatment (i.e sample is sufficient for stem cell analysis)
• Potentially fertile women must use an adequate method of contraception to avoid pregnancy throughout the study.
• Potentially fertile women must have a negative serum or urine pregnancy test

Exclusion Criteria:

• Fertile women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study
• Women who are pregnant or breastfeeding.
• Men with fertile sexual partners who can or will not use an acceptable contraception method for the entire study
• A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy.
• Known pleural effusion at baseline.
• Uncontrolled or significant cardiovascular disease
• History of significant bleeding disorder unrelated to CML, including:
• Prior chemotherapy for peripheral stem cell mobilization.
• Inadequate BM aspiration sample due to marrow fibrosis or other reasons
• Prior or concurrent malignancy
• Severe psychiatric illness, imprisonment or mental impairment inflicting on ability to give informed consent
• Abuse of alcohol, prescribed or illicit drugs
• Evidence of digestive dysfunction that would prevent administration of study therapy by mouth.

• Prohibited Treatments and/or Therapies

  • Any prior treatment with interferon
  • Any prior treatment with dasatinib
  • Any prior treatment with imatinib
  • Any other prior systemic treatments, with anti-CML activity [except for anagrelide, or hydroxyurea (HU)].
• Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes as described in Appendix 3.