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

NCT00101595 | Completed Phase 2

• 1 other identifier: CA180-015
• Study Type: interventional
• Target: 96
• Locations: 19 countries
• Sites: 59

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.

Conditions

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

Keywords

Lymphoid blast phase chronic myeloid leukemia; Philadelphia chromosome positive acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Major and overall hematologic response rates

  throughout the study

Secondary Outcomes (7)

• Durability of hematologic response and time to hematologic response (major and overall)

  throughout the study

• Assess cytogenetic and molecular responses

  throughout the study

• Measure minor hematologic response rate in the imatinib resistant group

  throughout the study

• Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene

  throughout the study

• Measure the heath-related QOL using FACT-G

  throughout the study

Study Arms (1)

1

EXPERIMENTAL

Drug: Dasatinib

Interventions

Dasatinib DRUG

Tablets, Oral, 70 mg, twice daily, Until disease progression or untolerable toxicity, switch to the roll-over study or study closure

Also known as: BMS-354825, Sprycel

1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (60)

Local Institution

Birmingham, Alabama, United States

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Anaheim, California, United States

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Los Angeles, California, United States

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Stanford, California, United States

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Vallejo, California, United States

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Jacksonville, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Kansas City, Kansas, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Hackensack, New Jersey, United States

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New York, New York, United States

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Portland, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Buenos Aires, Buenos Aires, Argentina

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Córdoba, Córdoba Province, Argentina

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St Leonards, New South Wales, Australia

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Vienna, Austria

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B-Leuven, Belgium

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Edegem, Belgium

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Yvoir, Belgium

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São Paulo, São Paulo, Brazil

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Campinas, Brazil

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Aarhus, Denmark

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Helsinki, Finland

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Lille, France

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Lyon, France

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Nantes, France

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Paris, France

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Pessac, France

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Poitiers, France

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Strasbourg, France

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Frankfurt am Main, Germany

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Hamburg, Germany

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Mainz, Germany

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Mannheim, Germany

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Ramat Gan, Israel

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Bologna, Italy

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Orbassano, Italy

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Roma, Italy

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Nijmegen, Netherlands

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Rotterdam, Netherlands

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Trondheim, Norway

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Lima, Lima Province, Peru

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Kyunggi-Do, South Korea

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Seoul, South Korea

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Gothenburg, Sweden

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Lund, Sweden

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Stockholm, Sweden

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Umeå, Sweden

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Uppsala, Sweden

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Basel, Switzerland

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Glasgow, Central, United Kingdom

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London, Greater London, United Kingdom

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Related Publications (3)

• 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.

  PMID: 17185463 BACKGROUND

• 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.

  PMID: 17496201 BACKGROUND

• 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.

  PMID: 18477770 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 12, 2005
• First Posted: January 13, 2005
• Study Start: January 1, 2005
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: April 14, 2011

Record last verified: 2011-04

Locations

PE (1); IL (1); GB (2); CH (1); FR (7); DE (4); DK (1); US (18); AU (1); BR (2); BE (3); NO (1); SE (5); KR (2); FI (1); AR (2); CA (2); IT (3); NL (2)