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

Study Overview
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Brief Summary
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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.

Detailed Description
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Design: Study Design and Duration as current described are no longer applicable since enrollment was prematurely concluded due to a decision by the sponsor.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: a maximum of 5 years after entry into the study until progression by Investigators determination/judgment intolerance to Dasatinib the study is terminated due to safety concerns or other administrative reasons as communicated by the sponsor Research Hypothesis : The research hypothesis and primary objective of this study as originally designed are no longer applicable as subjects enrolment has been terminated due to administrative reasons by the sponsor.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

Official Title
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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).

Conditions
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Leukemia

Intervention / Treatment
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* Drug: Dasatinib
* Drug: BMS-833923


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Dasatinib<br> | Drug: Dasatinib<br>* Tablets, Oral, 100 mg, Once daily, approximately 5 years depending on response<br>* Other names: Sprycel®;|
| Experimental: Arm2: Dasatinib + BMS-833923<br>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<br>* Tablets, Oral, 100 mg, Once daily, approximately 5 years depending on response<br>* Other names: Sprycel®;Drug: BMS-833923<br>* Capsules, Oral, dose to be determined, Once daily, approximately 2 years depending on response<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelogenous, Chronic, BCR-ABL Positive