Dasatinib (BMS-354825) in Subjects With Myeloid Blast Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate

NCT00101816 | Completed Phase 2 Results

• 1 other identifier: CA180-006
• Study Type: interventional
• Target: 124
• Locations: 19 countries
• Sites: 61

Brief Summary

The purpose of this study is to see what effect an investigational drug (BMS-354825) has on subjects who are currently in the myeloid blast phase of chronic myeloid leukemia (CML) and who are either resistant to or intolerant of imatinib mesylate. Another purpose of the study is to see what side effects this drug may have on subjects.

Conditions

Chronic Myeloid Leukemia; Blast Crisis

Keywords

Myeloid blast phase Chronic Myeloid Leukemia (CML)

Outcome Measures

Primary Outcomes (1)

• Major and Overall Hematologic Response (MaHR and OHR)

  MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. OHR=best confirmed response of MaHR or minor HR (MiHR). MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts + promyelocytes in bone marrow and \<30% blasts + promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea.

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

Secondary Outcomes (18)

• Median Duration of Major Hematologic Response (MaHR)

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

• Median Duration of Overall Hematologic Response (OHR)

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

• Time to MaHR and OHR

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

• Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response

  Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment

• Number of Participants With CHR or NEL, MiHR, or no Hematologic Response

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycles 1 and 2; After every 2nd cycle for Cycles 3+; at end of treatment

Study Arms (1)

1

EXPERIMENTAL

Drug: Dasatinib

Interventions

Dasatinib DRUG

Tablets, Oral, 70 mg, twice daily, Until disease progression or intolerable 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 myeloid blast phase chronic myeloid leukemia
• Subjects who are either resistant or intolerant of imatinib mesylate

You may not qualify if:

• Subjects who are eligible and willing to undergo transplantation
• Serious uncontrolled medical disorder or active infection
• Uncontrolled or significant heart problems, such as congestive heart failure, recent heart attack, etc
• Subjects receiving medications that may affect heart rhythm
• Other malignancy/cancer other than CML
• History of significant bleeding disorder unrelated to CML
• Pregnant or breastfeeding women (subjects must avoid becoming pregnant)
• Subjects received imatinib within 7 days, interferon or cytarabine within 14 days, a targeted anticancer medication within 14 days, an antineoplastic agent (other than hydroxyurea or anagrelide) within 28 days, or any other investigation medication in 28 days
• Subject is receiving medications that affect platelet function or an anticoagulant

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (62)

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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Denver, Colorado, 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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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, 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 Brunswick, 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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Seattle, Washington, United States

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Adelaide, South Australia, Australia

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Vienna, Austria

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B-Leuven, Belgium

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Edegem, Belgium

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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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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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Napoli, 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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Quezon City, Philippines

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Singapore, Singapore

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Jeollanam-Do, South Korea

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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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Umeå, Sweden

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Uppsala, Sweden

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Basel, Switzerland

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Taipei, Taiwan

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Taoyuan District, Taiwan

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Glasgow, Central, United Kingdom

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London, Greater London, United Kingdom

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Related Publications (2)

• 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

• 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; Blast Crisis

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; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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 13, 2005
• First Posted: January 14, 2005
• Study Start: December 1, 2004
• Primary Completion: August 1, 2006
• Study Completion: March 1, 2008
• Last Updated: August 10, 2010
• Results First Posted: March 2, 2010

Record last verified: 2010-06

Locations

NL (2); US (23); FI (1); GB (2); KR (3); AU (1); DE (3); IL (1); CA (1); FR (7); DK (1); PH (1); SG (1); SE (4); CH (1); TW (2); BE (2); NO (1); IT (4)