Low Dose Dasatinib (50 mg Daily) as First-line Treatment for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia

Randomized, Open-Label, Phase II, Multicenter, Multi-Country Study to Evaluate Safety and Efficacy of Dasatinib 50 mg in First-Line Treatment of Early Chronic Phase Chronic Myeloid Leukemia

The purpose of this multicenter randomized study is to compare efficacy and safety of dasatinib 50 mg once daily and dasatinib 100 mg once daily in patients with early chronic phase (CP) chronic myeloid leukemia (CML)

A multicenter, prospective, open-label, randomized Phase II study to compare efficacy by measuring rates of major molecular response (MMR) at 12 months in patients with Ph+ chronic phase (CP) chronic myeloid leukemia (CML) randomized to receive either dasatinib 50 mg QD or dasatinib 100 mg QD. Approximately 100 patients are expected to be randomized. The duration of patient participation will be 18 months

Inclusion Criteria:

1. Age ≥ 18 years.
2. Diagnosis of Ph+ or BCR-ABL positive CML in early CP (i.e. time from diagnosis <12 months). Except for hydroxyurea and/or 1-2 doses of cytarabine (up to 6g/m2 total), patients must have received no or minimal prior therapy, defined as 30 days of prior approved tyrosine kinase inhibitor (TKI).
3. Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph-chromosome has been historically included as a criterion of accelerated phase (AP). However, patients with clonal evolution as the only criterion of AP have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution and no other criteria for AP will be eligible for this study.
4. ECOG performance of 0-2.
5. Adequate end organ function defined as the following: total bilirubin <1.5x ULN (unless secondary to Gilbert's disease, in which case it should be <2.5x ULN), SGPT <2.5x ULN, creatinine <1.5x ULN.
6. Patients must sign an informed consent form (ICF) indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital

Exclusion Criteria:

1. NYHA cardiac class 3-4 heart disease

2. Cardiac symptoms - Patients meeting the following criteria are not eligible unless cleared by a cardiologist:

   1. Uncontrolled angina within 3 months
   2. Diagnosed or suspected congenital long QT syndrome
   3. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
   4. Prolonged QTc interval on pre-entry electrocardiogram (>460 msec)

3. History of significant bleeding disorder unrelated to cancer including:

   1. Diagnosed congenital bleeding disorders (e.g. Von Willebrand's disease)
   2. Diagnosed acquired bleeding disorder within one year (e.g. acquired anti-factor VIII antibodies)
   3. Isolated thrombocytopenia without recurrent bleeding episodes shall be considered eligible for study entry

4. Patients with active uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders

5. Women of pregnancy potential must practice an effective method of birth control, unless otherwise instructed, during the course of the study in a manner such that risk of failure is minimized

   1. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy
   2. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
   3. Women must continue birth control for the duration of the study and at least 3 months after the last dose of study drug

6. Pregnant or breast-feeding women are excluded

   a. All WOCBP must have a negative pregnancy test prior to first receiving the study drug. If the pregnancy test is positive, the patient must not receive the study drug and must not be enrolled in the study.

7. Patients in late chronic phase (i.e. time from diagnosis to treatment >12 months), accelerated phase (except as noted in inclusion criteria 2) or blast phase are excluded.