Phase 2 Dasatinib Combo With Smoothened (SMO) Antagonist (BMS-833923)

An Open-Label, Randomized, Multicenter Phase 2 Trial of Dasatinib (SPRYCEL®) vs. Dasatinib Plus Smoothened Antagonist (BMS-833923) in the Treatment of Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia (CML).

The purpose of the study is to compare response rates in newly diagnosed Chronic Phase (CP) CML subjects treated with dasatinib plus BMS-833923 versus dasatinib alone.

1. Design:

   Study Design and Duration as current described are no longer applicable since enrollment was prematurely concluded due to a decision by the sponsor. Subjects currently enrolled in the trial will continue to receive dasatinib alone at a starting dose of 100 mg QD for:

   1. a maximum of 5 years after entry into the study
   2. until progression by Investigators determination/judgment
   3. intolerance to Dasatinib
   4. the study is terminated due to safety concerns or
   5. other administrative reasons as communicated by the sponsor

2. Research Hypothesis :

The research hypothesis and primary objective of this study as originally designed are no longer applicable as subjects enrolment has been terminated due to administrative reasons by the sponsor. The objective of the altered design of this study is to describe the safety profile and tolerability of dasatinib

Inclusion Criteria:

• Subjects ≥ 18 years of age who have signed informed consent
• Philadelphia positive Chronic Myeloid Leukemia (CML) in chronic phase
• Previously untreated chronic phase CML, except for Anagrelide or Hydroxyurea.
• Eastern Co-Operative Group (ECOG) Performance Status (PS) Score 0 - 2

Exclusion Criteria:

• Known Abl-kinase T315I or T315A mutation
• Serious or uncontrolled medical disorder (including infection or cardiovascular disease) or dementia or other serious psychiatric condition
• Prior chemotherapy.
• Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy during the entire study period.