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Dasatinib (BMS-354825) in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Primary Purpose

Chronic Myeloid Leukemia, Leukemia, Lymphoblastic, Acute, Philadelphia-positive

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dasatinib
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Lymphoid blast phase chronic myeloid leukemia, Philadelphia chromosome positive acute lymphoblastic leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects with Philadelphia chromosome positive (Ph+) (BCR/ABL+) lymphoid blast phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate. Subjects who are considered to have lymphoid blast phase CML if they meet at least one of the following criteria: *30% lymphoid blasts in peripheral blood or bone marrow. *Extramedullary infiltrates of leukemic cells (other than in spleen or liver) with peripheral blood lymphoid blast morphology. ECOG performance status score 0-2. Adequate hepatic function defined as: *Total bilirubin less than or equal to 2.0 times the institutional upper limit of normal; *alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times the institutional upper limit of normal. Adequate renal function defined as: *serum creatinine less than or equal to 1.5 times the institutional upper normal limit. Men and women, 18 years of age or older. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IC/L or equivalent units of HCG) within 72 hours prior to the start of study medication. Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period of at least 1 month before and for at least 3 months after completion of the study medication. WOCBP using a prohibited contraceptive method (not applicable). Women who are pregnant or breastfeeding. Women with a positive pregnancy test on enrollment or prior to study drug administration. Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period and for at least 3 months after completion of study medication. Subjects who are eligible and willing to undergo transplantation during the screening period. A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy. Demential or altered mental status that would prohibit the understanding or rendering of informed consent. History of significant bleeding disorder unrelated to CML. Concurrent incurable malignancy other than CML. Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy. Subjects who received any of the following: imatinib mesylate within 7 days; interferon or cytarabine within 14 days; a targeted small molecule anti-cancer agent within 14 days; any other investigational or antineoplastic agent other than hydroxyurea or anagrelide within 28 days before starting treatment with BMS-354825. Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes. Subjects taking medications that irreversibly inhibit platelet function. Prior therapy with BMS-354825. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.

Sites / Locations

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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

Major and overall hematologic response rates

Secondary Outcome Measures

Durability of hematologic response and time to hematologic response (major and overall)
Assess cytogenetic and molecular responses
Measure minor hematologic response rate in the imatinib resistant group
Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene
Measure the heath-related QOL using FACT-G
To assess safety and tolerability of dasatinib
Population PK

Full Information

First Posted
January 12, 2005
Last Updated
April 7, 2011
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00101595
Brief Title
Dasatinib (BMS-354825) in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Official Title
A Phase II Study of BMS-354825 in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Resistant to or Intolerant of Imatinib Mesylate
Study Type
Interventional

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this clinical research study is to learn if BMS-354825 will have activity as defined by hematologic responses in subjects with lymphoid blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia with primary or acquired resistance to imatinib mesylate.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia, Leukemia, Lymphoblastic, Acute, Philadelphia-positive
Keywords
Lymphoid blast phase chronic myeloid leukemia, Philadelphia chromosome positive acute lymphoblastic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
BMS-354825, Sprycel
Intervention Description
Tablets, Oral, 70 mg, twice daily, Until disease progression or untolerable toxicity, switch to the roll-over study or study closure
Primary Outcome Measure Information:
Title
Major and overall hematologic response rates
Time Frame
throughout the study
Secondary Outcome Measure Information:
Title
Durability of hematologic response and time to hematologic response (major and overall)
Time Frame
throughout the study
Title
Assess cytogenetic and molecular responses
Time Frame
throughout the study
Title
Measure minor hematologic response rate in the imatinib resistant group
Time Frame
throughout the study
Title
Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene
Time Frame
throughout the study
Title
Measure the heath-related QOL using FACT-G
Time Frame
throughout the study
Title
To assess safety and tolerability of dasatinib
Time Frame
throughout the study
Title
Population PK
Time Frame
first month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with Philadelphia chromosome positive (Ph+) (BCR/ABL+) lymphoid blast phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate. Subjects who are considered to have lymphoid blast phase CML if they meet at least one of the following criteria: *30% lymphoid blasts in peripheral blood or bone marrow. *Extramedullary infiltrates of leukemic cells (other than in spleen or liver) with peripheral blood lymphoid blast morphology. ECOG performance status score 0-2. Adequate hepatic function defined as: *Total bilirubin less than or equal to 2.0 times the institutional upper limit of normal; *alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times the institutional upper limit of normal. Adequate renal function defined as: *serum creatinine less than or equal to 1.5 times the institutional upper normal limit. Men and women, 18 years of age or older. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IC/L or equivalent units of HCG) within 72 hours prior to the start of study medication. Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period of at least 1 month before and for at least 3 months after completion of the study medication. WOCBP using a prohibited contraceptive method (not applicable). Women who are pregnant or breastfeeding. Women with a positive pregnancy test on enrollment or prior to study drug administration. Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period and for at least 3 months after completion of study medication. Subjects who are eligible and willing to undergo transplantation during the screening period. A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy. Demential or altered mental status that would prohibit the understanding or rendering of informed consent. History of significant bleeding disorder unrelated to CML. Concurrent incurable malignancy other than CML. Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy. Subjects who received any of the following: imatinib mesylate within 7 days; interferon or cytarabine within 14 days; a targeted small molecule anti-cancer agent within 14 days; any other investigational or antineoplastic agent other than hydroxyurea or anagrelide within 28 days before starting treatment with BMS-354825. Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes. Subjects taking medications that irreversibly inhibit platelet function. Prior therapy with BMS-354825. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Birmingham
State/Province
Alabama
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United States
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Anaheim
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California
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United States
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Los Angeles
State/Province
California
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United States
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Stanford
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California
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United States
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Vallejo
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California
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United States
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Jacksonville
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Tampa
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Atlanta
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Georgia
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Chicago
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Illinois
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United States
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Kansas City
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Kansas
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United States
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Boston
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Massachusetts
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United States
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St. Louis
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Missouri
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United States
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Hackensack
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New Jersey
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United States
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New York
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New York
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United States
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Portland
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Oregon
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United States
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Pittsburgh
State/Province
Pennsylvania
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United States
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Nashville
State/Province
Tennessee
Country
United States
Facility Name
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Houston
State/Province
Texas
Country
United States
Facility Name
Local Institution
City
Buenos Aires
Country
Argentina
Facility Name
Local Institution
City
Cordoba
Country
Argentina
Facility Name
Local Institution
City
St. Leonards
State/Province
New South Wales
Country
Australia
Facility Name
Local Institution
City
Wien
Country
Austria
Facility Name
Local Institution
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B-Leuven
Country
Belgium
Facility Name
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Edegem
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Belgium
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Local Institution
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Yvoir
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Belgium
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Campinas
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Brazil
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Sao Paulo
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Brazil
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Toronto
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Ontario
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Canada
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Montreal
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Quebec
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Canada
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Aarhus
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Denmark
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Helsinki
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Finland
Facility Name
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Lille
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France
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Lyon Cedex 03
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France
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Nantes
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France
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Paris
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France
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Pessac
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France
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Poitiers Cedex
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France
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Strasbourg Cedex
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France
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City
Frankfurt/Main
Country
Germany
Facility Name
Local Institution
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Hamburg
Country
Germany
Facility Name
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Mainz
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Germany
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City
Mannheim
Country
Germany
Facility Name
Local Institution
City
Ramat-Gan
Country
Israel
Facility Name
Local Institution
City
Bologna
Country
Italy
Facility Name
Local Institution
City
Orbassano
Country
Italy
Facility Name
Local Institution
City
Roma
Country
Italy
Facility Name
Local Institution
City
Kyunggi-Do
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
Country
Korea, Republic of
Facility Name
Local Institution
City
Nijmegen
Country
Netherlands
Facility Name
Local Institution
City
Rotterdam
Country
Netherlands
Facility Name
Local Institution
City
Trondheim
Country
Norway
Facility Name
Local Institution
City
Lima
Country
Peru
Facility Name
Local Institution
City
Gothenburg
Country
Sweden
Facility Name
Local Institution
City
Lund
Country
Sweden
Facility Name
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Stockholm
Country
Sweden
Facility Name
Local Institution
City
Umea
Country
Sweden
Facility Name
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City
Uppsala
Country
Sweden
Facility Name
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City
Basel
Country
Switzerland
Facility Name
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City
Glasgow
State/Province
Central
Country
United Kingdom
Facility Name
Local Institution
City
London
State/Province
Greater London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
17185463
Citation
Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, Hochhaus A, Guilhot F, Saglio G, Apperley J, Ottmann O, Shah N, Erben P, Branford S, Agarwal P, Gollerkeri A, Baccarani M. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007 Apr 15;109(8):3207-13. doi: 10.1182/blood-2006-09-046888. Epub 2006 Dec 21.
Results Reference
background
PubMed Identifier
17496201
Citation
Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, Rege-Cambrin G, Radich J, Hochhaus A, Apanovitch AM, Gollerkeri A, Coutre S. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007 Oct 1;110(7):2309-15. doi: 10.1182/blood-2007-02-073528. Epub 2007 May 11.
Results Reference
background
PubMed Identifier
18477770
Citation
Porkka K, Koskenvesa P, Lundan T, Rimpilainen J, Mustjoki S, Smykla R, Wild R, Luo R, Arnan M, Brethon B, Eccersley L, Hjorth-Hansen H, Hoglund M, Klamova H, Knutsen H, Parikh S, Raffoux E, Gruber F, Brito-Babapulle F, Dombret H, Duarte RF, Elonen E, Paquette R, Zwaan CM, Lee FY. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood. 2008 Aug 15;112(4):1005-12. doi: 10.1182/blood-2008-02-140665. Epub 2008 May 13.
Results Reference
background

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Dasatinib (BMS-354825) in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

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