Study of BMS-354825 in Subjects With CML Who Are Resistant to or Intolerant of Imatinib or Ph+All in Japan

Study Overview
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Brief Summary
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This study is composed of Phase I and Phase II part. Phase I part: The objective is to evaluate the safety of BMS-354825 in subject with chronic phase Chronic Myelogenous Leukemia (CML). Dosage of BMS-354825 will be 50 mg BID, 70 mg BID or 90 mg BID. Phase II part: The objective is to evaluate the efficacy of BMS-354825. dosage will be decided according to the results of Phase I part. Treatment period will be 6 months for subjects with chronic phase CML, and 3 months for subjects with accelerated phase or blast phase CML and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)

Official Title
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A Phase I/II Study of BMS-354825 in Subjects With Imatinib Resistant or Intolerant Philadelphia Chromosome Positive Chronic Myelogenous Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Who Are Resistant or Intolerant to Treatment

Conditions
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Chronic Myelogenous Leukemia

Intervention / Treatment
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* Drug: Dasatinib
* Drug: Dasatinib
* Drug: Dasatinib
* Drug: Dasatinib
* Drug: Dasatinib
* Drug: Dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Philadelphia chromosome positive or bcr-abl gene positive Chronic Myelogenous Leukemia (CML) Subjects must have primary or acquired resistance to imatinib mesylate or have intolerance of imatinib mesylate Philadelphia Chromosome Positive Acute Lymphoblastic leukemia (Ph+ALL) Subjects must have primary or acquired resistance to chemotherapy or have intolerance of chemotherapy Performance status (general conditions) specified by the Eastern Cooperative Oncology Group: 0-2 Men and women, ages 20 - 75 Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized Exclusion Criteria: Subjects who are eligible and willing to undergo transplantation at pre-study Women who are pregnant or breastfeeding Uncontrolled or significant cardiovascular disease History of significant bleeding disorder unrelated to CML or ALL Adequate hepatic function Adequate renal function Medication that increase bleeding risk Medication that change heart rhythms Subjects who are compulsorily detained for legal reasons or treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1<br> | Drug: Dasatinib<br>* Tablets, Oral, 50mg BID, once daily, 24 weeks.<br>* Other names: Sprycel;|
| Experimental: A2<br> | Drug: Dasatinib<br>* Tablets, Oral, 70mg BID, once daily, 24 weeks.<br>* Other names: Sprycel;|
| Experimental: A3<br> | Drug: Dasatinib<br>* Tablets, Oral, 90mg BID, once daily, 24 weeks.<br>* Other names: Sprycel;|
| Experimental: B1<br> | Drug: Dasatinib<br>* Tablets, Oral, 70mg BID, once daily, 24 weeks.<br>* Other names: Sprycel;|
| Experimental: B2<br> | Drug: Dasatinib<br>* Tablets, Oral, 70mg BID, once daily, 12 weeks.<br>* Other names: Sprycel;|
| Experimental: B3<br> | Drug: Dasatinib<br>* Tablets, Oral, 70mg BID, once daily, 12 weeks.<br>* Other names: Sprycel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety of BMS-354825 administered orally twice daily for 4 weeks, evaluate the efficacy of BMS-354825 as defined by cytogenetic response for subjects with chronic phase CML, and as defined by hematologic response |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profiles, cytogenetic response and hematologic response, BCR-ABL point mutations and biochemical assays of BCR-ABL, safety, time to and duration of hematologic and cytogenetic response |  |  | 
| response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imatinib resistant or intolerant CML, Treatment resistant or intolerant Ph+ALL