Dasatinib Combination Therapy With the Smoothened (SMO) Inhibitor BMS-833923 in Chronic Myeloid Leukemia (CML)

Key Inclusion Criteria

* Age ≥18 years
* Diagnosis of chronic myeloid leukemia (CML) and cytogenetic positive for the Philadelphia chromosome (Ph+), documented Ph+ cells on bone marrow assessment (BMA) ≤6 weeks prior to treatment
* Either chronic-phase CML, with \<15% blasts in peripheral blood and bone marrow, or advanced-phase CML, including Ph+ acute lymphoblastic leukemia (ALL) (\> 5% blasts) or hematologic progression with ≥15% blasts not in complete cytogenetic remission
* Resistance or suboptimal response to imatinib, dasatinib, or nilotinib and no known T315I/A Abl-kinase mutation.

Key Exclusion Criteria

* Known Abl-kinase T315I or T315A mutation
* CCyR at baseline
* Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
* Uncontrolled or significant cardiovascular disease
* Grade 3 or higher peripheral blood counts
* Serum calcium or phosphate below the lower limit of normal
* Baseline hypomagnesemia and amylase or lipase at least Grade 1 or higher
* Reduced renal function, defined as serum creatinine level \>3\*upper limit of normal
* Prior therapies for CML or Ph+ ALL permitted, with the following restriction:

  * Therapy permitted with corticosteroids, hydroxyurea, or anagrelide prior to starting treatment and during the first 4 weeks on study
  * 6 months or longer after stem cell transplantation
  * 28 days or longer after any investigational agent
  * 7 days or longer after any standard chemotherapy agent
  * Concomitant use of medications with a known risk of causing Torsades de Pointes
  * Concomitant use of strong inhibitors of the CYP3A4 isoenzyme