Phase 2 Dasatinib Combo With Smoothened (SMO) Antagonist (BMS-833923)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01357655
Recruitment Status : Terminated (No participants enrolled in this trial could receive the SMO antagonist as a recommended phase 2 dose was not determined by a different, concurrently-run trial.)
First Posted : May 23, 2011
Results First Posted : March 14, 2017
Last Update Posted : March 14, 2017
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of the study is to compare response rates in newly diagnosed Chronic Phase (CP) CML subjects treated with dasatinib plus BMS-833923 versus dasatinib alone.

Condition or disease Intervention/treatment Phase
Leukemia Drug: Dasatinib Drug: BMS-833923 Phase 2

Detailed Description:
  1. Design:

    Study Design and Duration as current described are no longer applicable since enrollment was prematurely concluded due to a decision by the sponsor. Subjects currently enrolled in the trial will continue to receive dasatinib alone at a starting dose of 100 mg QD for:

    1. a maximum of 5 years after entry into the study
    2. until progression by Investigators determination/judgment
    3. intolerance to Dasatinib
    4. the study is terminated due to safety concerns or
    5. other administrative reasons as communicated by the sponsor
  2. Research Hypothesis :

The research hypothesis and primary objective of this study as originally designed are no longer applicable as subjects enrolment has been terminated due to administrative reasons by the sponsor. The objective of the altered design of this study is to describe the safety profile and tolerability of dasatinib

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Multicenter Phase 2 Trial of Dasatinib (SPRYCEL®) vs. Dasatinib Plus Smoothened Antagonist (BMS-833923) in the Treatment of Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia (CML).
Study Start Date : September 2011
Actual Primary Completion Date : January 2016
Actual Study Completion Date : January 2016

Arm Intervention/treatment
Active Comparator: Arm 1: Dasatinib Drug: Dasatinib
Tablets, Oral, 100 mg, Once daily, approximately 5 years depending on response
Other Name: Sprycel®

Experimental: Arm2: Dasatinib + BMS-833923
Dasatinib for 1 year followed by dasatinib plus BMS-833923 for 2 years followed by dasatinib alone for approximately 2 years; depending on response
Drug: Dasatinib
Tablets, Oral, 100 mg, Once daily, approximately 5 years depending on response
Other Name: Sprycel®

Drug: BMS-833923
Capsules, Oral, dose to be determined, Once daily, approximately 2 years depending on response

Primary Outcome Measures :
  1. Number of Participants With Major Molecular Response [ Time Frame: Baseline up to 12 months ]
    Major molecular response (MMR) was assessed using BCR-ABL transcript levels measured by real-time quantitative polymerase chain reaction (qPCR). MMR was defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value). Number of participants with MMR by timepoint are cumulative.

Secondary Outcome Measures :
  1. Complete Molecular Response at Any Time [ Time Frame: Baseline to End of study (approximately 48 months) ]
  2. Progression-free Survival, Measured by the Time From Start of Treatment to Progression or Death [ Time Frame: Baseline to End of study (approximately 48 months) ]
  3. Event-free Survival, Measured by the Time From Start of Treatment to Progression, Death or Treatment Discontinuation [ Time Frame: Baseline to End of study (approximately 48 months) ]
  4. Transformation-free Survival Measured by the Time From Start of Treatment to Criteria for Accelerated or Blast Phase CML Are Met and Death [ Time Frame: Baseline to End of study (approximately 48 months) ]
  5. Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death [ Time Frame: From date of first dose of study treatment up to the date of the last dose plus 30 days (approximately 49 months) ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects ≥ 18 years of age who have signed informed consent
  • Philadelphia positive Chronic Myeloid Leukemia (CML) in chronic phase
  • Previously untreated chronic phase CML, except for Anagrelide or Hydroxyurea.
  • Eastern Co-Operative Group (ECOG) Performance Status (PS) Score 0 - 2

Exclusion Criteria:

  • Known Abl-kinase T315I or T315A mutation
  • Serious or uncontrolled medical disorder (including infection or cardiovascular disease) or dementia or other serious psychiatric condition
  • Prior chemotherapy.
  • Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy during the entire study period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01357655

United States, New Jersey
John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
United States, Tennessee
Tennessee Oncology Pllc
Nashville, Tennessee, United States, 37203
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Local Institution
San Miguel De Tucuman, Tucuman, Argentina, 4000
Local Institution
Antwerpen, Belgium, 2060
Local Institution
Brugge, Belgium, B-8000
Canada, Alberta
Local Institution
Edmonton, Alberta, Canada, T6G 1Z2
Local Institution
Helsinki, Finland, 00290
Local Institution
Nantes, Cedex, France, 44000
Local Institution
Bordeaux, France, 33076
Local Institution
Le Chesnay, France, 78150
Local Institution
Lille, France, 59037
Local Institution
Paris Cedex 10, France, 75475
Local Institution
Strasbourg Cedex, France, 67091
Local Institution
Toulouse Cedex 09, France, 31059
Local Institution
Chorzow, Poland, 41-500
Local Institution
Gdansk, Poland, 80-952
Local Institution
Krakow, Poland, 30-510
Local Institution
Lodz, Poland, 93-513
Local Institution
Wroc#aw, Poland, 50-367
Local Institution
Madrid, Spain, 28006
Local Institution
Madrid, Spain, 28034
Local Institution
Oviedo, Spain, 33006
Local Institution
Pamplona, Spain, 31008
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Responsible Party: Bristol-Myers Squibb Identifier: NCT01357655     History of Changes
Other Study ID Numbers: CA180-363
2011-000083-10 ( EudraCT Number )
First Posted: May 23, 2011    Key Record Dates
Results First Posted: March 14, 2017
Last Update Posted: March 14, 2017
Last Verified: January 2017

Keywords provided by Bristol-Myers Squibb:
BCR-ABL Positive

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action