Clinical trial NCT01218477: Dasatinib Combination Therapy With the Smoothened (SMO) Inhibitor BMS-833923 in Chronic Myeloid Leukemia (CML)
Official title: Dasatinib (BMS-354825) Combined With SMO Inhibitor (BMS-833923; XL139) in CML With Resistance or Suboptimal Response to a Prior TKI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Keywords: Leukemia
(Chronic Myeloid Leukemia-Chronic Phase and Advanced)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-10-11
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


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 \<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

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D) of BMS-833923 Plus Dasatinib in Chronic Myeloid Leukemia-Chronic Phase
timeFrame: Day 1 to Week 80, with observation for DLT in Weeks 5-8
Secondary outcomes:
measure: 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)
timeFrame: Day 1 to Week 80
measure: 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)
timeFrame: Day 1 to Week 80
measure: 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
timeFrame: Day 1 to Week 80, continuously, with observation for dose-limiting toxicities (DLTs) in Weeks 5-8
measure: Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
timeFrame: Day 1 to Week 80
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University Of California Medical Center
state: California
city: Baltimore
country: United States
facility: Sidney Kimmel Cancer Center At Johns Hopkins
state: Maryland
city: Houston
country: United States
facility: Ut M.D. Anderson Cancer Center
state: Texas
city: Hamilton
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Helsinki
country: Finland
facility: Local Institution
city: Bordeaux
country: France
facility: Local Institution
city: Poitiers Cedex
country: France
facility: Local Institution
city: Frankfurt/main
country: Germany
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Orbassano(To)
country: Italy
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: