Study of Dasatinib in Patients With Chronic Phase Chronic Myeloid Leukemia and a Suboptimal Response to Imatinib

Leukemia, Myeloid, Chronic Clinical Trial

Official title:

An Open-label, Randomized Study of Dasatinib vs High-dose (800-mg) Imatinib in the Treatment of Subjects With Chronic Phase Chronic Myeloid Leukemia Who Have Had a Suboptimal Response After at Least 3 Months of Therapy With 400 mg Imatinib

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00320190
• Other study ID #: CA180-043
• Secondary ID: EUDRACT Number:
• Status: Terminated
• Phase: Phase 2
• First received: May 1, 2006
• Last updated: October 1, 2013
• Start date: August 2006
• Est. completion date: January 2010

Study information

• Verified date: July 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy of dasatinib with that of high-dose (800-mg) imatinib in participants with chronic phase chronic myeloid leukemia who achieved only a suboptimal response after at least 3 months of monotherapy with 400-mg imatinib. The safety of these treatments will also be evaluated.

Description:

Participants were randomized 2:1 to dasatinib or high-dose imatinib, respectively. Randomization was stratified by a suboptimal response, defined as a hematologic response less than a complete hematologic response after at least 3 months of monotherapy with 400-mg imatinib; a cytogenic response (CgR) less than a partial CgR (PCgR) after at least 6 months of monotherapy with 400-mg; a PCgR after at least 12 months of monotherapy with 400-mg imatinib; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with 400-mg imatinib.

Participants received either dasatinib or imatinib for 12 months or until disease progression, unacceptable toxicity, consent withdrawal, or study discontinuation. After 12 months, who had a confirmed major molecular response and were still receiving dasatinib, 100 mg, or imatinib, 800 mg, were eligible to extend treatment for an additional 12 months. Participants permanently discontinuing treatment before 12 months were considered treatment failures and withdrawn from the study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 52
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic phase Ph^+ chronic myeloid leukemia (CML) demonstrating only a suboptimal response, defined as a hematologic response that is less than a complete hematologic response after at least 3 months of monotherapy with imatinib, 400 mg; a cytogenic response (CgR) that is less than a partial CgR (PCgR) after at least 6 months of monotherapy with imatinib, 400 mg; a PCgR after at least 12 months of monotherapy with imatinib, 400 mg; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with imatinib, 400 mg.

• Either gender

• Age of 18 years or older

Exclusion Criteria:

• Previous diagnosis of accelerated phase or blast crisis CML

• Uncontrolled or significant cardiovascular disease

• History of significant bleeding disorder unrelated to CML

• Concurrent malignancies

• Intolerance of imatinib, 400 mg

• Prior treatment with imatinib at a dose higher than 400 mg

• Prior stem cell transplantation and/or high-dose chemotherapy for CML

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic
• Leukemia, Myeloid, Chronic-Phase

Intervention

Drug:
• Imatinib
Imatinib tablets administered orally at a dose of 400 mg twice daily. Each 400- mg dose to be taken with a meal and a large glass of water.
• Dasatinib
Dasatinib tablets administered orally at a dose of 100 mg once daily.

Locations

Country	Name	City	State
Belgium	Local Institution	Antwerpen
Belgium	Local Institution	Charleroi
Finland	Local Institution	Helsinki
Finland	Local Institution	Tampere
France	Local Institution	Lyon Cedex 03
France	Local Institution	Marseille Cedex 9
France	Local Institution	Montpellier Cedex 5
France	Local Institution	Paris Cedex 10
France	Local Institution	Rennes
France	Local Institution	Strasbourg Cedex
France	Local Institution	Toulouse Cedex 09
Germany	Local Institution	Leipzig
Italy	Local Institution	Orbassano (To)
Norway	Local Institution	Oslo
Norway	Local Institution	Trondheim
Portugal	Local Institution	Lisboa
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	St.Petersburg
Spain	Local Institution	Murcia
Sweden	Local Institution	Lund
Sweden	Local Institution	Orebro
Sweden	Local Institution	Uppsala
United Kingdom	Local Institution	Glasgow	Central
United Kingdom	Local Institution	Leeds	North Yorkshire
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	London	Greater London

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

Belgium,  Finland,  France,  Germany,  Italy,  Norway,  Portugal,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR)	MMolR is defined as reduction in transcript levels of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene of at least 3 log. The BCR-ABL gene has a role in the production of a mutated protein that converts bone marrow stem cells from normal to leukemic.	At 12 months from baseline	No
Secondary	Percentage of Participants With Death as Outcome, Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, and AEs Leading to Discontinuation	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose results in death, persistent or significant disability/incapacity, drug dependency, or drug abuse; prolongs inpatient hospitalization; or is life-threatening, a congenital anomaly/birth defect, or an important medical event. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.	Months 1 to 12, continuously, and Months 12 to 24, continuously	Yes
Secondary	Percentage of Participants With On-study AEs of Special Interest	GI=gastrointestinal. AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. Grade 1=mild; Grade 2=moderate; Grade 3=severe and undesirable; Grade 4=life-threatening or disabling; Grade 5=death. Percentages based on the number of participants with a specific grade at baseline. Participants without on-study test values for a particular laboratory analyte are not included in the reporting of that analyte.	Months 1 to 12, continuously, and Months 12 to 24, continuously	Yes
Secondary	Median Time to MMolR	Time to MMolR is defined as the time from first treatment dose until measurement criteria are first met for MMolR. MMolR is defined as a reduction in transcript levels of the BCR-ABL gene of at least 3 log from baseline.	At 3, 6, 9, and 12 months from baseline	No
Secondary	Percentage of Participants With Complete Cytogenetic Response	Cytogenetic response is based on the prevalence of Ph+ metaphases among cells in metaphase in a bone marrow sample.	At 6 and 12 months from baseline	No
Secondary	Median Time to Treatment Failure	Time to treatment failure is defined as the time in days from randomization to progressive disease documented by the investigator, to death from any cause without prior progression, or to early treatment discontinuation for any reason, whichever occurs first. Participants without disease progression or who do not die and complete the 12-month study treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.	Randomization to disease progression, death, or discontinuation (to 12 months)	No
Secondary	Median Time to Progression-free Survival	Progression-free survival is defined as the time in days from randomization to progressive disease documented by the investigator or to death from any cause without prior progression. Participants without progressive disease or who do not die and complete the 12-month treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.	Randomization to disease progression or death (to 12 months)	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form