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

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).

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.

Study Overview

• Status: Terminated
• Conditions: Leukemia
• Intervention / Treatment: Drug: Dasatinib; Drug: BMS-833923

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   Study Design and Duration as current described are no longer applicable since enrollment was prematurely concluded due to a decision by the sponsor.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The research hypothesis and primary objective of this study as originally designed are no longer applicable as subjects enrolment has been terminated due to administrative reasons by the sponsor.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
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, 4000
      • Local Institution
• Belgium
  • Antwerpen, Belgium, 2060
    • Local Institution
  • Brugge, Belgium, B-8000
    • Local Institution
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution
• Finland
  • Helsinki, Finland, 00290
    • Local Institution
• France
  • 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
  • Cedex
    • Nantes, Cedex, France, 44000
      • Local Institution
• Poland
  • 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
• Spain
  • Madrid, Spain, 28034
    • Local Institution
  • Madrid, Spain, 28006
    • Local Institution
  • Oviedo, Spain, 33006
    • Local Institution
  • Pamplona, Spain, 31008
    • Local Institution
• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Dasatinib	Drug: Dasatinib; Tablets, Oral, 100 mg, Once daily, approximately 5 years depending on response; Other Names: 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 Names: Sprycel®; Drug: BMS-833923; Capsules, Oral, dose to be determined, Once daily, approximately 2 years depending on response

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Major Molecular Response	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.	Baseline up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Molecular Response at Any Time		Baseline to End of study (approximately 48 months)
Progression-free Survival, Measured by the Time From Start of Treatment to Progression or Death		Baseline to End of study (approximately 48 months)
Event-free Survival, Measured by the Time From Start of Treatment to Progression, Death or Treatment Discontinuation		Baseline to End of study (approximately 48 months)
Transformation-free Survival Measured by the Time From Start of Treatment to Criteria for Accelerated or Blast Phase CML Are Met and Death		Baseline to End of study (approximately 48 months)
Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death	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.	From date of first dose of study treatment up to the date of the last dose plus 30 days (approximately 49 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: May 18, 2011
• First Submitted That Met QC Criteria: May 19, 2011
• First Posted (Estimate): May 23, 2011

Study Record Updates

• Last Update Posted (Actual): March 14, 2017
• Last Update Submitted That Met QC Criteria: January 24, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Chronic; BCR-ABL Positive; Myelogenous
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: CA180-363; 2011-000083-10 (EudraCT Number)