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Chronic Myeloid LeukemiaPhase 2NCT00103844

Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia

A Phase 2 study testing Dasatinib and Imatinib in people with Chronic Myeloid Leukemia and Philadelphia-Positive Myeloid Leukemia, run by Bristol-Myers Squibb at 131 sites in 32 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary purpose of this study is to estimate the major cytogenetic response rates of BMS-354825 and imatinib (800 mg/d) in subjects with chronic phase, Philadelphia chromosome positive, chronic myeloid leukemia (PH+ CML) with disease resistant to imatinib at a dose of 400-600 mg/d. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dasatinib and Imatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
131 sitesin 32 countries
Study dates
Feb 2005to Mar 2008
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women, 18 years of age or older.
  • Subjects with Chronic Phase Ph+ CML.
  • Subjects have not been treated with imatinib at a dose >600 mg/day.
  • Subjects developed resistance to disease while receiving an imatinib dose 400-600 mg/day.
  • Able to tolerate imatinib at the highest dose the subject had received in the past.
  • Demonstrate adequate renal and hepatic function.
  • Women of childbearing potential must have a negative serum or urine pregnancy test, must be using an adequate method of contraception.

Who cannot join

  • Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period for a least 1 month before and at least 3 months after the completion of the study.
  • Women using a prohibited contraceptive method.
  • Women who are pregnant or breastfeeding.
  • Men whose sexual partners are women who are of childbearing potential, and who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period as outlined above.
  • Prior treatment with imatinib at a dose >600 mg/day.
  • Subjects who have previously identified specific BCR-ABL mutations.
Show all 20Show fewer
  • Previous diagnosis of accelerated phase or blast crisis CML.
  • Intolerance to imatinib at any dose.
  • Subjects who are eligible and willing to undergo transplantation during the screening period.
  • Serious uncontrolled medical disorder or active infection.
  • Uncontrolled or significant cardiovascular disease.
  • Uncontrolled hypertension.
  • Dementia or altered mental status.
  • Evidence of organ dysfunction.
  • Use of imatinib within 7 days.
  • Use of interferon or cytarabine within 14 days.
  • Use of a targeted small molecule anticancer agent within 14 days.
  • Subjects taking certain medications that are accepted to have a risk of causing Torsades de Pointes.
  • Subjects taking medications that irreversibly inhibit platelet function or anticoagulants.
  • Prior therapy with BMS-354825.

Trial locations and contacts

131 sites in 32 countries.

131 sites in 32 countries

United States53 sites
  • Local Institution

    Anaheim, California

  • Local Institution

    Athens, Georgia

  • Local Institution

    Atlanta, Georgia

  • Local Institution

    Aurora, Colorado

  • Local Institution

    Bakersfield, California

  • Local Institution

    Birmingham, Alabama

  • Local Institution

    Boston, Massachusetts

  • Local Institution

    Cary, North Carolina

  • Local Institution

    Chapel Hill, North Carolina

  • Local Institution

    Chicago, Illinois

  • Local Institution

    Columbia, Missouri

  • Local Institution

    Dallas, Texas

  • Local Institution

    Fort Worth, Texas

  • Local Institution

    Fullerton, California

  • Local Institution

    Greenville, South Carolina

  • Local Institution

    Hackensack, New Jersey

  • Local Institution

    Hartford, Connecticut

  • Local Institution

    Houston, Texas

  • Local Institution

    Indianapolis, Indiana

  • Local Institution

    Jacksonville, Florida

  • Local Institution

    Kansas City, Kansas

  • Local Institution

    Kansas City, Missouri

  • Local Institution

    Lawrenceville, Georgia

  • Local Institution

    Lexington, Kentucky

  • Local Institution

    Loma Linda, California

  • Local Institution

    Los Angeles, California

  • Local Institution

    Minneapolis, Minnesota

  • Local Institution

    Monterey Park, California

  • Local Institution

    Morristown, New Jersey

  • Local Institution

    Nashville, Tennessee

  • Local Institution

    New Brunswick, New Jersey

  • Local Institution

    Norfolk, Virginia

  • Local Institution

    Oklahoma City, Oklahoma

  • Local Institution

    Omaha, Nebraska

  • Local Institution

    Peoria, Illinois

  • Local Institution

    Pittsburgh, Pennsylvania

  • Local Institution

    Portland, Oregon

  • Local Institution

    Rochester, Minnesota

  • Local Institution

    San Antonio, Texas

  • Local Institution

    San Diego, California

  • Local Institution

    Santa Barbara, California

  • Local Institution

    Santa Maria, California

  • Local Institution

    Seattle, Washington

  • Local Institution

    Spokane, Washington

  • Local Institution

    St Louis, Missouri

  • Local Institution

    Stanford, California

  • Local Institution

    Tampa, Florida

  • Local Institution

    Tucker, Georgia

  • Local Institution

    Tulsa, Oklahoma

  • Local Institution

    Tyler, Texas

  • Local Institution

    Vallejo, California

  • Local Institution

    Vancouver, Washington

  • Local Institution

    Washington D.C., District of Columbia

Other trials in United States

France7 sites
  • Local Institution

    Lille

  • Local Institution

    Lyon

  • Local Institution

    Nantes

  • Local Institution

    Paris

  • Local Institution

    Pessac

  • Local Institution

    Poitiers

  • Local Institution

    Strasbourg

Other trials in France

Belgium6 sites
  • Local Institution

    B-Leuven

  • Local Institution

    Bruges

  • Local Institution

    Brussels

  • Local Institution

    Charleroi

  • Local Institution

    Edegem

  • Local Institution

    Yvoir

Other trials in Belgium

Germany6 sites
  • Local Institution

    Dresden

  • Local Institution

    Groenkloof

  • Local Institution

    Hamburg

  • Local Institution

    Leipzig

  • Local Institution

    Mainz

  • Local Institution

    Mannheim

Other trials in Germany

Italy6 sites
  • Local Institution

    Bari

  • Local Institution

    Bologna

  • Local Institution

    Milan

  • Local Institution

    Naples

  • Local Institution

    Orbassano

  • Local Institution

    Roma

Other trials in Italy

Australia5 sites
  • Local Institution

    Adelaide, South Australia

  • Local Institution

    Camperdown, New South Wales

  • Local Institution

    Perth, Western Australia

  • Local Institution

    South Brisbane, Queensland

  • Local Institution

    St Leonards, New South Wales

Other trials in Australia

Sweden5 sites
  • Local Institution

    Gothenburg

  • Local Institution

    Lund

  • Local Institution

    Stockholm

  • Local Institution

    Umeå

  • Local Institution

    Uppsala

Other trials in Sweden

Canada4 sites
  • Local Institution

    Edmonton, Alberta

  • Local Institution

    Montreal, Quebec

  • Local Institution

    Toronto, Ontario

  • Local Institution

    Vancouver, British Columbia

Other trials in Canada

Poland4 sites
  • Local Institution

    Katowice

  • Local Institution

    Krakow

  • Local Institution

    Lublin

  • Local Institution

    Warsaw

Other trials in Poland

Brazil3 sites
  • Local Institution

    Curitiba, Paraná

  • Local Institution

    Rio de Janeiro, Rio de Janeiro

  • Local Institution

    São Paulo, São Paulo

Other trials in Brazil

South Africa3 sites
  • Local Institution

    Bloemfontein, Free State

  • Local Institution

    Parktown, Gauteng

  • Local Institution

    Soweto, Gauteng

Other trials in South Africa

United Kingdom3 sites
  • Local Institution

    Glasglow, Central

  • Local Institution

    London, Greater London

  • Local Institution

    Newcastle, Tyne and Wear

Other trials in United Kingdom

Argentina2 sites
  • Local Institution

    Buenos Aires, Buenos Aires

  • Local Institution

    Córdoba, Córdoba Province

Other trials in Argentina

China2 sites
  • Local Institution

    Beijing

  • Local Institution

    Shanghai

Other trials in China

Russia2 sites
  • Local Institution

    Moscow

  • Local Institution

    Saint Petersburg

Other trials in Russia

Spain2 sites
  • Local Institution

    Barcelona

  • Local Institution

    Madrid

Other trials in Spain

Switzerland2 sites
  • Local Institution

    Basel

  • Local Institution

    Bellinzona

Other trials in Switzerland

Taiwan2 sites
  • Local Institution

    Taipei

  • Local Institution

    Taoyuan

Other trials in Taiwan

Austria1 site
  • Local Institution

    Wein

Other trials in Austria

Denmark1 site
  • Local Institution

    Aarhus

Other trials in Denmark

Estonia1 site
  • Local Institution

    Tallinn

Other trials in Estonia

Finland1 site
  • Local Institution

    Helsinki

Other trials in Finland

Hungary1 site
  • Local Institution

    Budapest

Other trials in Hungary

Ireland1 site
  • Local Institution

    Dublin

Other trials in Ireland

Israel1 site
  • Local Institution

    Ramat Gan

Other trials in Israel

Norway1 site
  • Local Institution

    Trondheim

Other trials in Norway

Peru1 site
  • Local Institution

    Lima, Lima Province

Other trials in Peru

Philippines1 site
  • Local Institution

    Quezon City

Other trials in Philippines

Puerto Rico1 site
  • Local Institution

    San Juan

Other trials in Puerto Rico

Singapore1 site
  • Local Institution

    Singapore

Other trials in Singapore

South Korea1 site
  • Local Institution

    Kyunggi-Do

Other trials in South Korea

Thailand1 site
  • Local Institution

    Bangkok

Other trials in Thailand

About this study

Official title: A Randomized Multi-Center Open Label Study of BMS-354825 vs. Imatinib Mesylate (Gleevec) 800 mg/d in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to Imatinib at a Dose at 400 - 600 mg/d

The primary purpose of this study is to estimate the major cytogenetic response rates of BMS-354825 and imatinib (800 mg/d) in subjects with chronic phase, Philadelphia chromosome positive, chronic myeloid leukemia (PH+ CML) with disease resistant to imatinib at a dose of 400-600 mg/d.

Being tested
Dasatinib, Imatinib
Keywords
Chronic Phase Philadelphia chromosome Positive (Ph+) chronic myeloid leukemia
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DasatinibDrug

    Also called Sprycel, BMS-354825

    Tablets, oral, 20 mg and 50mg, twice daily, up to 96 weeks

  • ImatinibDrug

    Tablets, Oral, 400mg and 100mg, twice daily, up to 96 weeks

Study groups in NCT00103844
Study groupRoleWhat they receive
1ExperimentalActive Comparator
Receives: Drug: Dasatinib
2ExperimentalActive Comparator
Receives: Drug: Imatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Major Cytogenetic Response (MCyR) at Week 12

    Cytogenetic response was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (CCyR; 0% Ph+ cells in metaphase in bone marrow) or Partial CyR (PCyR; >0% to 35% Ph+ cells in metaphase in bone marrow).

    Measured: Week 12

Secondary outcomes (13)
  1. MCyR at Any Time Prior to Crossover

    Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as CCyR (0% Ph+ cells in metaphase in bone marrow) or PCyR (>0% to 35% Ph+ cells in metaphase in bone marrow).

    Measured: Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements.

  2. Duration of MCyR at 12 Months and 18 Months

    Percentage of participants who achieved MCyR and did not progress at 12 and 18 months.

    Measured: 12 months, 18 months

  3. Duration of MCyR at 24 Months

    Percentage of participants who achieved MCyR and did not progress at 24 months.

    Measured: 24 Months

  4. Time to MCyR Prior to Crossover

    Median time from first dosing date to date of MCyR

    Measured: Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements.

  5. Complete Hematologic Response (CHR) at Any Time Prior to Crossover

    Participants achieving CHR prior to crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

    Measured: Baseline (within 4 weeks of Day 1), weekly until Week 12 and then every 12 weeks until crossover or off-study; restricted to precrossover measurements.

  6. Duration of Complete Hematologic Response (CHR)

    Percentage of participants who achieved CHR and did not progress at specified time points. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

    Measured: 12 months, 24 months

  7. Time to CHR Prior to Crossover

    Median time from first dosing date to date of CHR. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

    Measured: Baseline (within 4 weeks of Day 1), weekly until Week 12, then every 12 weeks until crossover or off-study; restricted to precrossover measurements.

  8. Major Molecular Response (MMR)

    Number of participants Achieving MMR. MMR is defined as ≤3 log reduction (ie, international ratio ≤0.1), in BCR-ABL levels from the standardized baseline value of BCR-ABL: Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL: Control gene ratio by the lab-specific conversion factor.

    Measured: Pretreatment, then after every 4 weeks for 12 weeks, then after every 12 week period out to 2 years; restricted to precrossover measurements.

  9. CHR After Crossover

    Participants achieving CHR after crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

    Measured: Weekly for 12 weeks, then after every 12 week period out to 2 years; restricted to postcrossover measurements.

  10. Cytogenetic Response After Crossover

    Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (0% Ph+ cells in metaphase in bone marrow) or Partial CyR (>0% to 35% Ph+ cells in metaphase in bone marrow).

    Measured: every 12 week period out to 2 years and off-study timepoints; restricted to postcrossover measurements

  11. Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover

    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

    Measured: Continuously from baseline through 2 years

  12. Health-Related Quality of Life Prior to Crossover

    Health-related quality of life as measured by Functional Assessment of Cancer Therapy-General (FACT-G). FACT-G=27 questions in 4 domains: physical, social/family, emotional, \& functional well-being (PWB, SWB, EWB, FWB). Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, \& FWB score change of 3 or more, \& SWB score change of 2 or more=minimal clinical important change.

    Measured: Every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment. Last questionnaire was to be completed at first follow-up visit after off-study date.

  13. Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib

    Number of participants from which blood samples were collected for population PK studies.

    Measured: Day 8: pretreatment trough sample, a sample between 30 minutes and 3 hours following treatment, a sample between 5 and 8 hours following treatment, and a sample at 12 hours, prior to the next dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2005 (estimated)
  2. Study startFeb 2005
  3. Primary completionAug 2006
  4. Study completionMar 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00103844
Sponsor's protocol ID
CA180-017
Status last verified
Jun 2010
First submitted
15 Feb 2005
Last updated
10 Aug 2010
Data monitoring committee
No

Publications

  • Kantarjian H, Pasquini R, Levy V, Jootar S, Holowiecki J, Hamerschlak N, Hughes T, Bleickardt E, Dejardin D, Cortes J, Shah NP. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: two-year follow-up of a randomized phase 2 study (START-R). Cancer. 2009 Sep 15;115(18):4136-47. doi: 10.1002/cncr.24504.

    PubMed 19536906
  • Muller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, Branford S, Hughes TP, Radich JP, Ploughman L, Mukhopadhyay J, Hochhaus A. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009 Dec 3;114(24):4944-53. doi: 10.1182/blood-2009-04-214221. Epub 2009 Sep 24.

    PubMed 19779040

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dasatinib and Imatinib in people with Chronic Myeloid Leukemia and Philadelphia-Positive Myeloid Leukemia, run by Bristol-Myers Squibb at 131 sites in 32 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 131 sites in United States, France, Belgium, Germany, Italy and 27 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Major Cytogenetic Response (MCyR) at Week 12 (time frame: Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00103844, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2010.

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