Status:

COMPLETED

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

Lead Sponsor:

Bristol-Myers Squibb

Conditions:

Leukemia

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

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

Inclusion

  • 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

Exclusion

    Key Trial Info

    Start Date :

    January 1 2011

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    April 1 2013

    Estimated Enrollment :

    33 Patients enrolled

    Trial Details

    Trial ID

    NCT01218477

    Start Date

    January 1 2011

    End Date

    April 1 2013

    Last Update

    June 17 2016

    Active Locations (12)

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    Page 1 of 3 (12 locations)

    1

    University Of California Medical Center

    San Francisco, California, United States, 94143

    2

    Sidney Kimmel Cancer Center At Johns Hopkins

    Baltimore, Maryland, United States, 21287

    3

    Ut M.D. Anderson Cancer Center

    Houston, Texas, United States, 77030

    4

    Local Institution

    Hamilton, Ontario, Canada, L8N 3Z5