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

• Status: Completed
• Trial end date: 2013-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to determine the safety and tolerability of the combination of BMS-833923 plus dasatinib in patients with chronic myeloid leukemia.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bristol-Myers Squibb
• Treatments: Dasatinib

Criteria

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