Phase 2
Completed N=27
Dasatinib Combination Therapy With the Smoothened (SMO) Inhibitor BMS-833923 in Chronic Myeloid Leukemia (CML)
Source: ClinicalTrials.gov NCT01218477 ↗Enrolled (actual)
27
Serious AEs
33.3%
Results posted
May 2014
Primary outcomePrimary: Recommended Phase 2 Dose (RP2D) of BMS-833923 Plus Dasatinib in Chronic Myeloid Leukemia-Chronic Phase — 50 mg
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Recommended Phase 2 Dose (RP2D) of BMS-833923 Plus Dasatinib in Chronic Myeloid Leukemia-Chronic Phase |
50 | — |
| SECONDARY Percentage of Participants With a Major Cytogenetic Response (MCyR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP) |
66.7; 20; 66.7 | — |
| SECONDARY Percentage of Participants With a Major Hematologic Response (MHR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP) |
50; 60; 100 | — |
| SECONDARY Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities |
1; 0; 2; 0; 1; 3 | — |
| SECONDARY Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results |
0; 0; 5; 0; 0; 0 | — |
Eligibility 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 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
Data sourced from ClinicalTrials.gov (NCT01218477). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.