A Phase III Study of Dasatinib vs. Imatinib in Patients With Newly Diagnosed Chronic Phase CML

Myeloid Leukemia, Chronic Clinical Trial

— DASISION  

Official title:

An Open-Label, Randomized, Multicenter Phase III Trial of Dasatinib (SPRYCEL®) vs. Standard Dose Imatinib (400 mg) in the Treatment of Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00481247
• Other study ID #: CA180-056
• Secondary ID: 2006-005712-27
• Status: Completed
• Phase: Phase 3
• First received: May 30, 2007
• Last updated: September 25, 2014
• Start date: August 2007
• Est. completion date: December 2013

Study information

• Verified date: September 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationIndia: Central Drugs Standard Control OrganizationGreece: National Organization of MedicinesSingapore: Clinical Trials & Epidemiology Research Unit (CTERU)Japan: Pharmaceuticals and Medical Devices AgencyTurkey: Ministry of HealthChina: Food and Drug AdministrationSouth Korea: Korea Food and Drug Administration (KFDA)Czech Republic: State Institute for Drug ControlHungary: National Institute of PharmacyPoland: National Institute of MedicinesRussia: Ministry of Health of the Russian FederationAustria: Federal Office for Safety in Health CareGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Spain: Spanish Agency of MedicinesArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: National Health Surveillance AgencyChile: CONEPColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosPeru: Instituto Nacional de SaludMexico: Federal Commission for Sanitary Risks ProtectionDenmark: Danish Dataprotection AgencyItaly: Ministry of HealthBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical research study is to compare the rate of confirmed complete cytogenetic response (cCCyR) of dasatinib to imatinib therapy within 12 months after randomization in newly diagnosed chronic phase Philadelphia positive chronic myeloid leukemia (Ph+ CML) patients. The safety of this treatment will also be studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 515
• Est. completion date: December 2013
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Male & Female =18 years

• Chronic Phase Ph+ CML

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score 0-2

Exclusion Criteria:

• Pleural Effusion

• Uncontrolled cardiovascular (CV) disease

• Significant bleeding disorder unrelated to CML

• Prior treatment with interferon/imatinib/dasatinib/anti-CML systemic treatments except anagrelide/hydroxyurea

Study Design

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

Related Conditions & MeSH terms

• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Myeloid Leukemia, Chronic
• Philadelphia Chromosome

Intervention

Drug:
• Dasatinib
Tablets, oral, dasatinib 50-140 mg once daily (QD)
• Imatinib
Tablets, oral, imatinib 200-800 mg, QD

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Australia	Local Institution	Brisbane	Queensland
Australia	Local Institution	Greenslopes	Queensland
Australia	Local Institution	Perth	Western Australia
Australia	Local Institution	Waratah	New South Wales
Austria	Local Institution	Innsbruck
Austria	Local Institution	Wien
Belgium	Local Institution	Brugge
Belgium	Local Institution	Bruxelles
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Jau	Sao Paulo
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Chile	Local Institution	Santiago	Metropolitana
China	Local Institution	Beijing	Beijing
China	Local Institution	Fuzhou	Fujian
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Tianjin	Tianjin
Colombia	Local Institution	Bogota
Colombia	Local Institution	Colombia	Bogota
Czech Republic	Local Institution	Brno
Czech Republic	Local Institution	Hradec Kralove
Czech Republic	Local Institution	Olomouc
Czech Republic	Local Institution	Prague 2
Denmark	Local Institution	Aarhus
France	Local Institution	Brest Cedex 02
France	Local Institution	Lille Cedex
France	Local Institution	Limoges
France	Local Institution	Montpellier Cedex
France	Local Institution	Nantes	Cedex 1
France	Local Institution	Paris
France	Local Institution	Paris Cedex 10
France	Local Institution	Pierre Benite Cedex
France	Local Institution	Poitiers Cedex
France	Local Institution	Rennes
France	Local Institution	Strasbourg Cedex
France	Local Institution	Toulouse Cedex 09
France	Local Institution	Vandoeuvre Les Nancy
Germany	Local Institution	Berlin
Germany	Local Institution	Rostock
Germany	Local Institution	Tuebingen
Germany	Local Institution	Ulm
Greece	Local Institution	Thessaloniki
Hungary	Local Institution	Budapest
Hungary	Local Institution	Debrecen
India	Local Institution	Ahmedabad
India	Local Institution	Cochin
India	Local Institution	Mumbai
India	Local Institution	Mumbai
India	Local Institution	Mumbai
India	Local Institution	Trivandrum
India	Local Institution	Vellore	Tamilnadu
Italy	Local Institution	Bologna
Italy	Local Institution	Catania
Italy	Local Institution	Monza (mb)
Italy	Local Institution	Orbassano (to)
Italy	Local Institution	Pavia
Italy	Local Institution	Roma
Italy	Local Institution	Roma
Japan	Local Institution	Bunkyo-ku	Tokyo
Japan	Local Institution	Fukuoka-shi	Fukuoka
Japan	Local Institution	Kagoshima-shi	Kagoshima
Japan	Local Institution	Kamogawa-shi	Chiba
Japan	Local Institution	Kyoto-shi	Kyoto
Japan	Local Institution	Morioka-shi	Iwate
Japan	Local Institution	Nagoya	Aichi
Japan	Local Institution	Okayama-shi	Okayama
Japan	Local Institution	Osaka-shi	Osaka
Japan	Local Institution	Sendai	Miyagi
Japan	Local Institution	Shinagawa-ku	Tokyo
Japan	Local Institution	Yokohama	Kanagawa
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Culiacan	Sinaloa
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Mexico D.f.	Distrito Federal
Mexico	Local Institution	Mexico, D. F.	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Netherlands	Local Institution	Groningen
Netherlands	Local Institution	Nijmegen
Peru	Local Institution	Arequipa
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Poland	Local Institution	Chorzow
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Poznan
Poland	Local Institution	Warsaw
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Rostov-on-don
Russian Federation	Local Institution	St.petersburg
Singapore	Local Institution	Singapore
Spain	Local Institution	A Coruna
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga
Spain	Local Institution	Oviedo
Spain	Local Institution	Salamanca
Spain	Local Institution	Valencia
Turkey	Local Institution	Ankara
Turkey	Local Institution	Kayseri
United States	Molecular Md	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Chile,  China,  Colombia,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Poland,  Russian Federation,  Singapore,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Grade 3/4 AEs, Drug-related Fluid Retention AEs (FRAEs), Drug-related Serious Adverse Events(SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths	Grade 3=Severe, Grade 4=Life-threatening or disabling. AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.	Participants were followed for at least 5 years	Yes
Other	Number of Participants With Grade 3/4 On Study Laboratory Abnormalities	Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil: grade 3 < 1000-500/mm^3; grade 4 < 500/mm^3. Hemoglobin: grade 3 < 8.0-6.5 g/dL; grade 4 < 6.5 g/dL. Platelets: grade 3 < 50,000-25,000/mm^3; grade 4 < 25,000/mm^3. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST): grade 3 >5.0-20 x ULN (upper limit of normal), grade 4 > 20 x ULN. Total Bilirubin: grade 3 > 3-10 x ULN; grade 4 > 10x ULN. Sample normal ranges (may vary by institution): ALT, Female: 7-30 U/L, Male: 10-55 U/L; AST, Female: 9-25 U/L, Male10-40 U/L; Total Bilirubin: total 0.0-1.0 mg/dL	Participants were followed for at least 5 years	Yes
Primary	Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months	Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from Bone Marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A confirmed cytogenetic response (cCCyR)=those in which all measurements up to at least 28 days after the initial response show an equivalent or better complete cytogenetic response.	Pre-treatment, every 3 months up to 12 months	No
Secondary	Time-in Confirmed cCCyR at Any Time	Time-in cCCyR at any time was computed for all randomized subjects. For subjects with cCCyR at any time, it is measured from the time measurement criteria are first met for CCyR(provided it is confirmed later) until the date of progression or death. Subjects with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Subjects without cCCyR are considered to have progressed on day 1.	Every 3 months for 2 years, then once per year for 3 years and/ or once per year for subjects in confirmed complete cytogenetic response at any timepoint or investigator's decision	No
Secondary	Number of Participants With Major Molecular Response (MMR) at Any Time	Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction (RQ-PCR). A major molecular response (MMR) is defined as a ratio BCR-ABL/ABL =0.1% on the international scale (i.e., at least 3 log reduction from a standardized baseline value).	Pre-treatment, every 3 months for 2 years, then every 6 months for 3 years	No
Secondary	Time to Confirmed CCyR Overall	The Time-to cCCyR for participants with cCCyR is defined as the time from the randomization date until criteria are first met for CCyR (provided it is confirmed later). The time-to cCCyR for all randomized subjects censors non-responders who do not progress at their cytogenetic assessments and non-responders who progress at the maximum time of all randomized subjects.	Every 3 months for 2 years, then once per year for 3 years and/ or once per year for subjects in confirmed complete cytogenetic response at any timepoint	No
Secondary	Time to MMR Overall	The Time-to MMR for participants with MMR is defined as the time from randomization date until measurement criteria are first met for MMR. The time-to MMR for all randomized subjects censor non-responders who do not progress at their last molecular assessments and non-responders who progress at the maximum time of all randomized subjects.	Every 3 months for 2 years, then every 6 months for 3 years	No
Secondary	Percentage of Participants With Progression-free Survival (PFS) at 12 Months	PFS=time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date & after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized.	Participants were followed for at least 5 years	No
Secondary	Percentage of Participants With Overall Survival (OS) at 12 Months	Overall survival (OS) was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive.	Participants were followed for at least 5 years	No

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