AzTrials
AzTrials

Chronic Myeloid LeukemiaPhase 2NCT00101660

Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib

A Phase 2 study testing Dasatinib in people with Chronic Myeloid Leukemia and Philadelphia-Positive Myeloid Leukemia, run by Bristol-Myers Squibb at 85 sites in 22 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 purpose of this study is assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dasatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
387 participants
Where
85 sitesin 22 countries
Study dates
Feb 2005to Apr 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

  • Age of 18 years and older.
  • Chronic myeloid leukemia (CML)
  • Previous treatment with imatinib at a dose of >600 mg/day AND the development of progressive disease while receiving imatinib at that dose, OR
  • CML with resistance to imatinib at a dose less than or equal to 600 mg/day with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib, OR
  • Intolerance to imatinib at any dose
  • Adequate organ function
  • Women who are able to bear children must have a negative serum or urine pregnancy test. Adequate methods of contraception must be used throughout the study to avoid pregnancy for the entire interval of at least 1 month before and 3 months after completion of the study medication.

Who cannot join

  • Woman 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
  • Previous diagnosis of accelerated phase or blast crisis CML.
  • Participants who are eligible and willing to undergo transplantation during the screening period
  • Uncontrolled or significant cardiovascular disease
  • Use of imatinib within 7 days.
Show all 10Show fewer
  • Use of interferon or cytarabine within 14 days
  • Use of a targeted small-molecule anticancer agent within 14 days
  • Use of certain medication that carry a known side effect risk of Torsade de Pointes - Certain medications that irreversibly inhibit platelet function or anticoagulants
  • Prior therapy with dasatinib.

Trial locations and contacts

85 sites in 22 countries.

85 sites in 22 countries

United States32 sites
  • Local Institution

    Anaheim, California

  • Local Institution

    Atlanta, Georgia

  • Local Institution

    Baltimore, Maryland

  • Local Institution

    Boston, Massachusetts

  • Local Institution

    Chicago, Illinois

  • Local Institution

    Dallas, Texas

  • Local Institution

    Detroit, Michigan

  • 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

    Loma Linda, California

  • Local Institution

    Los Angeles, California

  • Local Institution

    Nashville, Tennessee

  • Local Institution

    New Brunswick, New Jersey

  • Local Institution

    New York, New York

  • Local Institution

    Omaha, Nebraska

  • Local Institution

    Philadelphia, Pennsylvania

  • Local Institution

    Pittsburgh, Pennsylvania

  • Local Institution

    Portland, Oregon

  • Local Institution

    San Antonio, Texas

  • Local Institution

    Spokane, Washington

  • Local Institution

    St Louis, Missouri

  • Local Institution

    Stanford, California

  • Local Institution

    Tampa, Florida

  • Local Institution

    Tyler, Texas

  • Local Institution

    Vallejo, California

  • 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

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

    East Mebourne, Victoria

  • Local Institution

    Parkville, Victoria

  • 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

Belgium4 sites
  • Local Institution

    B-Leuven

  • Local Institution

    Brussels

  • Local Institution

    Edegem

  • Local Institution

    Yvoir

Other trials in Belgium

Germany4 sites
  • Local Institution

    Hamburg

  • Local Institution

    Leipzig

  • Local Institution

    Mainz

  • Local Institution

    Mannheim

Other trials in Germany

Canada3 sites
  • Local Institution

    Montreal, Quebec

  • Local Institution

    Toronto, Ontario

  • Local Institution

    Vancouver, British Columbia

Other trials in Canada

Ireland2 sites
  • Local Institution

    Co Galway, Galway

  • Local Institution

    Dublin

Other trials in Ireland

Netherlands2 sites
  • Local Institution

    Nijmegen

  • Local Institution

    Rotterdam

Other trials in Netherlands

South Africa2 sites
  • Local Institution

    Parktown, Gauteng

  • Local Institution

    Soweto, Gauteng

Other trials in South Africa

Spain2 sites
  • Local Institution

    Barcelona

  • Local Institution

    Madrid

Other trials in Spain

United Kingdom2 sites
  • Local Institution

    Glasgow, Central

  • Local Institution

    London, Greater London

Other trials in United Kingdom

Austria1 site
  • Local Institution

    Wein

Other trials in Austria

Denmark1 site
  • Local Institution

    Aarhus

Other trials in Denmark

Finland1 site
  • Local Institution

    Helsinki

Other trials in Finland

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

Singapore1 site
  • Local Institution

    Singapore

Other trials in Singapore

South Korea1 site
  • Local Institution

    Kyunggi-Do

Other trials in South Korea

Switzerland1 site
  • Local Instituion

    Basel

Other trials in Switzerland

About this study

Official title: A Phase II Study to Determine the Activity of BMS-354825 in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to High Dose Imatinib Mesylate (Gleevec) or Who Are Intolerant of Imatinib

The purpose of this study is assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Other purposes of the study are to identify any side effects the drug may produce and to study the level of dasatanib in the blood and assess the efficacy of dasatanib in the treatment of leukemia.

Being tested
Dasatinib
Keywords
Chronic phase Philadelphia chromosome chronic myeloid leukemia (Ph+CML)
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

    Tablets; oral; 70 mg BID, depending on response

Study groups in NCT00101660
Study groupRoleWhat they receive
Dasatinib, 70 mg twice daily (BID)ExperimentalDasatanib, 70 mg twice daily (BID), with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance.
Receives: Drug: Dasatinib

What is being measured

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

  1. Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)

    Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases.

    Measured: 2 years

Secondary outcomes (11)
  1. Number of Imatinib-intolerant Participants With MCyR

    Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.

    Measured: Baseline to 2 years

  2. Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months

    Based on the Kaplan-Meier estimate of the duration of response. Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases.

    Measured: 12 and 24 Months

  3. Median Time From First Dosing Date to Date of MCyR

    MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.

    Measured: Baseline (within 4 weeks of Day 1) and every 12 weeks

  4. Number of Participants With Complete Hematologic Response (CHR)

    CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.

    Measured: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study

  5. Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months

    Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.

    Measured: 12 and 24 months

  6. Median Time From First Dosing Until CHR

    CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.

    Measured: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study

  7. Number of Participants With Major Molecular Response (MMR)

    MMR is defined as ≤3 log reduction 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: Baseline to 2 years

  8. Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores

    Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. 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, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics.

    Measured: Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.

  9. Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE

    AE=any new untoward medical occurrence or worsening of a preexisting 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

  10. Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE

    AE=any new untoward medical occurrence or worsening of a preexisting 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

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

    Blood samples were collected for PK to be included in separate population PK analyses.

    Measured: Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours 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 posted13 Jan 2005 (estimated)
  2. Study startFeb 2005
  3. Primary completionSep 2006
  4. Study completionApr 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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
387 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00101660
Sponsor's protocol ID
CA180-013
Status last verified
Feb 2012
First submitted
12 Jan 2005
Last updated
2 Mar 2012
Data monitoring committee
No

Publications

  • Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, Facon T, Goldberg SL, Cervantes F, Niederwieser D, Silver RT, Stone RM, Hughes TP, Muller MC, Ezzeddine R, Countouriotis AM, Shah NP. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007 Mar 15;109(6):2303-9. doi: 10.1182/blood-2006-09-047266. Epub 2006 Nov 30.

    PubMed 17138817
  • 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 in people with Chronic Myeloid Leukemia and Philadelphia-Positive Myeloid Leukemia, run by Bristol-Myers Squibb at 85 sites in 22 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 10 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 2 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 85 sites in United States, France, Italy, Australia, Sweden and 17 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 24 Feb 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 Imatinib-resistant Participants With Major Cytogenetic Response (MCyR) (time frame: 2 years). 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 NCT00101660, 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 2 Mar 2012.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in