Pediatric Philadelphia Positive Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Dasatinib when added to standard chemotherapy is effective and safe in the treatment of pediatric philadelphia chromosome positive acute lymphoblastic leukemia

Official Title
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A Phase 2 Multi-Center, Historically Controlled Study of Dasatinib Added to Standard Chemotherapy in Pediatric Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Conditions
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Leukemia, Pediatric

Intervention / Treatment
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* Drug: Dasatinib


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Newly diagnosed Philadelphia chromosome positive Acute Lymphoblastic Leukemia (ALL) Age >1 year and < less than 18 years old Induction chemotherapy ≤ 14 days according to institutional standard of care Adequate liver, renal and cardiac function Exclusion Criteria: Prior treatment with a Oncogene fusion protein (BCR-ABL) inhibitor Extramedullary involvement of the testicles Active systemic bacterial, fungal or viral infection Down syndrome

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Dasatinib<br> | Drug: Dasatinib<br>* Tablets, Oral, 60 mg/m2, Once daily, 2 years or until unacceptable toxicity<br>* Other names: Sprycel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Event-free Survival (EFS) Rate | 3-year EFS rate is defined as the percentage of participants without event after 3 years since the start of study treatment. Events for EFS are defined as ANY first one of the following: Lack of complete response in bone marrow Relapse at any site Development of second malignant neoplasm Death from any cause | From first dose to 3 years following first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events | Number of participants experiencing different types of all causality all grade adverse events | From first dose to 100 days following last dose (up to approximately 23 months) | 
| Event-Free Survival (EFS) Rate (Kaplan-Meier Estimates) | Overall estimation of the EFS of dasatinib plus chemotherapy was performed utilizing the Kaplan-Meier (KM) Product Limit method. The 3-year and 5-year EFS rates were computed with the corresponding 95% CI's using Greenwood's formula. Analyses of EFS included KM plots with number of patients at risk. Participants who neither relapse nor die or who are lost to follow-up were censored on the date of their last bone marrow, CSF assessment or physical exam, whichever occurred last. | From first dose to 3 years or 5 years following first dose | 
| Complete Remission Rate | Complete Remission rate is defined as the percentage of participants achieving a complete remission, i.e. < 5% lymphoblasts in bone marrow and in CSF, with no evidence of other extramedullary disease. Complete remission will be assessed at the end of Induction IA, end of induction IB and end of the consolidation period for all treated participants. | From first dose to End of Induction Period Ia (up to 5 weeks) or Ib (up to 9 weeks) or End of Consolidation Period (up to 22 weeks) | 
| Percentage of Participants Negative for Minimal Residual Disease (MRD) | MRD was by real-time qPCR for clone-specific immunoglobulin and T-cell receptor gene rearrangements (IG/TCR). Participants were declared as MRD negative if the MRD level is undetectable providing the assay lower limit of quantification is at least 0.1% | From first dose to End of Induction Period Ia (up to 5 weeks) or Ib (up to 9 weeks) or End of Consolidation Period (up to 22 weeks) | 
| Percentage of Participants With BCR-ABL Mutations at Baseline and at Time of Disease Progression or Relapse | A BCR-ABL mutation is defined as the presence of a detectable amino acid substitution in the ABL kinase domain, assessed by Real-time quantitative PCR. | At baseline (prior to start of study treatment) and at disease progression or relapse (up to approximately 3 years) |