Study of Dasatinib (BMS-354825) in Patients With Accelerated Phase Chronic Myeloid Leukemia

NCT00101647 | Completed Phase 2 Results

• 1 other identifier: CA180-005
• Study Type: interventional
• Target: 197
• Locations: 23 countries
• Sites: 70

Brief Summary

The purpose of this clinical research study is to learn if BMS-354825 will have activity, defined by hematologic response, in subjects who have accelerated phase chronic myeloid leukemia (CML) who are resistant to or intolerant to imatinib mesylate. The safety of this treatment will also be studied.

Conditions

Chronic Myelogenous Leukemia

Keywords

Chronic myelogenous leukemia (CML): Accelerated phase

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). OHR=best confirmed response of MaHR or minor hematologic response (MiHR). Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea. Maintaining a response=no 2 consecutive records of nonresponse at assessment. Criteria for CHR and NEL specified in Outcome Measure 2 and criteria for MiHR in Outcome Measure 4.

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment

Secondary Outcomes (16)

• Percentage of Participants Who Achieved MaHR and Did Not Progress at 12 Months (Based on the Kaplan-Meier Estimate of the Duration of Response)

  12 months

• Percentage of Participants Who Achieved MaHR and Did Not Progress at 24 Months in the Imatinib-Resistant Group (Based on the Kaplan-Meier Estimate of the Duration of Response)

  24 months

• Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months

  12 months, 24 months

• Median Time in Days From First Dosing Date to Date of MaHR

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment

• Time to OHR

  Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; 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 Philadelphia chromosome positive (PH+) or the fused gene BCR/ABL positive (BCR/ABL+) accelerated phase chronic myeloid leukemia (CML) whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate.
• Subjects must have had prior exposure to imatinib. However, imatinib mesylate does not need to be their most recent CML treatment prior to coming on this study.
• Men and women, 18 years of age or older.
• Adequate hepatic function.
• Adequate renal function.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized.

You may not qualify if:

• Women who are pregnant or breastfeeding.
• 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 subjects to receive protocol therapy.
• Uncontrolled or significant cardiovascular disease.
• Medications that increase bleeding risk.
• Medications that change heart rhythms.
• Dementia 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.
• Prior therapy with dasatinib (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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (70)

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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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 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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Dallas, Texas, 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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South Brisbane, Queensland, Australia

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East Melbourne, Victoria, Australia

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Parkville, Victoria, Australia

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Wien, Australia

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B-Leuven, Belgium

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Edegem, Belgium

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Rio de Janeiro, Rio de Janeiro, Brazil

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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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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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Lima, Lima Province, Peru

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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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Bangkok, Thailand

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Glasgow, Central, United Kingdom

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London, Greater London, United Kingdom

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Related Publications (2)

• Guilhot F, Apperley J, Kim DW, Bullorsky EO, Baccarani M, Roboz GJ, Amadori S, de Souza CA, Lipton JH, Hochhaus A, Heim D, Larson RA, Branford S, Muller MC, Agarwal P, Gollerkeri A, Talpaz M. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007 May 15;109(10):4143-50. doi: 10.1182/blood-2006-09-046839. Epub 2007 Jan 30.

  PMID: 17264298 BACKGROUND

• Apperley JF, Cortes JE, Kim DW, Roy L, Roboz GJ, Rosti G, Bullorsky EO, Abruzzese E, Hochhaus A, Heim D, de Souza CA, Larson RA, Lipton JH, Khoury HJ, Kim HJ, Sillaber C, Hughes TP, Erben P, Van Tornout J, Stone RM. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial. J Clin Oncol. 2009 Jul 20;27(21):3472-9. doi: 10.1200/JCO.2007.14.3339. Epub 2009 Jun 1.

  PMID: 19487385 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase

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

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 12, 2005
• First Posted: January 13, 2005
• Study Start: December 1, 2004
• Primary Completion: August 1, 2006
• Study Completion: March 1, 2008
• Last Updated: April 15, 2011
• Results First Posted: March 2, 2010

Record last verified: 2011-04

Locations

TH (1); BR (3); FR (7); IT (4); SG (1); SE (4); US (21); GB (2); AR (2); AU (5); DE (3); TW (2); KR (3); FI (1); DK (1); NO (1); NL (2); PH (1); CA (1); PE (1); BE (2); IL (1); CH (1)