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

NCT01357655 | Terminated Phase 2 Results

• 2 other identifiers: CA180-3632011-000083-10
• Study Type: interventional
• Target: 70
• Locations: 8 countries
• Sites: 24

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.

Conditions

Leukemia

Keywords

Myelogenous; Chronic; BCR-ABL Positive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

  From date of first dose of study treatment up to the date of the last dose plus 30 days (approximately 49 months)

Study Arms (2)

Arm 1: Dasatinib

ACTIVE COMPARATOR

Drug: Dasatinib

Arm2: Dasatinib + BMS-833923

EXPERIMENTAL

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; Drug: BMS-833923

Interventions

Dasatinib DRUG

Tablets, Oral, 100 mg, Once daily, approximately 5 years depending on response

Also known as: Sprycel®

Arm 1: Dasatinib; Arm2: Dasatinib + BMS-833923

BMS-833923 DRUG

Capsules, Oral, dose to be determined, Once daily, approximately 2 years depending on response

Arm2: Dasatinib + BMS-833923

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (24)

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Tennessee Oncology Pllc

Nashville, Tennessee, 37203, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Local Institution

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Local Institution

Antwerp, 2060, Belgium

Location

Local Institution

Bruges, B-8000, Belgium

Location

Local Institution

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution

Helsinki, 00290, Finland

Location

Local Institution

Nantes, Cedex, 44000, France

Location

Local Institution

Bordeaux, 33076, France

Location

Local Institution

Le Chesnay, 78150, France

Location

Local Institution

Lille, 59037, France

Location

Local Institution

Paris, 75475, France

Location

Local Institution

Strasbourg, 67091, France

Location

Local Institution

Toulouse, 31059, France

Location

Local Institution

Chorzów, 41-500, Poland

Location

Local Institution

Gdansk, 80-952, Poland

Location

Local Institution

Krakow, 30-510, Poland

Location

Local Institution

Lodz, 93-513, Poland

Location

Local Institution

Wroc#aw, 50-367, Poland

Location

Local Institution

Madrid, 28006, Spain

Location

Local Institution

Madrid, 28034, Spain

Location

Local Institution

Oviedo, 33006, Spain

Location

Local Institution

Pamplona, 31008, Spain

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Leukemia; Bronchiolitis Obliterans Syndrome

Interventions

Dasatinib; BMS-833923

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

No recommended phase 2 dose of the SMO antagonist was determined (in a separate trial). It was decided to discontinue enrollment and end this trial early. The decision was not made due to any new safety signals for dasatinib or the SMO antagonist.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2011
• First Posted: May 23, 2011
• Study Start: September 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: March 14, 2017
• Results First Posted: March 14, 2017

Record last verified: 2017-01

Locations

BE (2); ES (4); AR (1); FR (7); FI (1); US (3); CA (1); PL (5)