Clinical trial NCT01593254: Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib
Official title: An Open Label, Randomized (2:1) Phase IIb Study of Dasatinib Versus Imatinib in Patients With Chronic Phase Chronic Myeloid Leukemia Who Have Not Achieved an Optimal Response to 3 Months of Therapy With 400 mg Imatinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Phase Chronic Myeloid Leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: ICON Clinical Research
name: PPD Development, LP
name: Molecular MD
name: MultiPharma
name: Q2 Solutions
name: Donald E. Morisky
name: MD Anderson Symptom Inventory (MDASI-CML)
name: OBiS, Inc
name: Steering Committee
First posted: 2012-05-08
Enrollment: 262
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the hypothesis that patients with CML who have not achieved optimal response after 3 months of treatment with imatinib will have a better response by switching to dasatinib compared to staying on their original imatinib regimen.


Eligibility criteria: Inclusion Criteria:

* Chronic Phase (CP)-CML Ph+ patients with complete hematologic response (CHR) but without one log BCR-ABL reduction (BCR-ABL level \>10% IS) 3 months of imatinib 400mg treatment. (Imatinib transient dose adjustments due to Adverse Event (AEs) are allowed with a maximum of 2 weeks interruption of treatment with imatinib (cumulative) within the 3 month period before randomization). Imatinib monotherapy must have been started within 6 months of CP-CML diagnosis (Ph + /BCR-ABL detection)
* Currently tolerating imatinib 400mg QD. Patients with prior imatinib treatment interruption or dose reductions are required to be on treatment with 400 mg imatinib for two weeks immediately prior to randomization to ensure tolerance to imatinib
* Eastern Co-Operative Group (ECOG) performance status = 0 - 2
* Adequate renal function defined as serum creatinine ≤3 times the institutional upper limit of normal (ULN)
* Adequate hepatic function defined as: total bilirubin ≤2.0 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the institutional ULN

Exclusion Criteria:

* Previous diagnosis of accelerated phase or blast crisis
* Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases at baseline bone marrow cytogenetic test, unless the same abnormalities were present at diagnosis. Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are eligible for the study
* Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after initial achievement
* Documented T315I/A, F317L, or V299L mutations (if already available - not required for screening)
* A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy

Primary outcomes:
measure: Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment
timeFrame: At 12 months after Day 1 initiation of 1st line treatment with imatinib or imatinib at any dose, after less than optimal response to first-line imatinib.
Secondary outcomes:
measure: Median Time to Major Molecular Response (MMR)
timeFrame: From randomization to study completion. Approximately 115 months
measure: Time to Molecular Response (MR)^4.5
timeFrame: From randomization to study completion. Approximately 115 months
measure: Progression Free Survival (PFS)
timeFrame: From randomization to study completion. Approximately 115 months
measure: Overall Survival (OS)
timeFrame: From randomization to study completion. Approximately 115 months
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Local Institution - 0004
state: California
city: Fontana
country: United States
facility: Local Institution - 0006
state: California
city: Los Angeles
country: United States
facility: University Of Southern California University Hospital
state: California
city: Roseville
country: United States
facility: Local Institution - 0110
state: California
city: San Jose
country: United States
facility: Local Institution - 0112
state: California
city: Vallejo
country: United States
facility: Local Institution - 0009
state: California
city: Whittier
country: United States
facility: Local Institution - 0078
state: California
city: Southington
country: United States
facility: Local Institution - 0089
state: Connecticut
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Crown Point
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health
state: Indiana
city: Iowa City
country: United States
facility: University Of Iowa
state: Iowa
city: Rochester
country: United States
facility: Local Institution - 0010
state: Minnesota
city: Cincinnati
country: United States
facility: Local Institution - 0002
state: Ohio
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution - 0001
state: Tennessee
city: Houston
country: United States
facility: Michael E Debakey VAMC
state: Texas
city: Laredo
country: United States
facility: Institute of Oncology Hematology Biomedical Research
state: Texas
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center
state: West Virginia
city: Milwaukee
country: United States
facility: Local Institution - 0005
state: Wisconsin
city: La Plata
country: Argentina
facility: Local Institution - 0093
state: Buenos Aires
city: Ramos Mejia
country: Argentina
facility: Local Institution - 0080
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Local Institution - 0049
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Local Institution - 0051
city: Buenos Aires
country: Argentina
facility: Local Institution - 0057
city: Corrientes
country: Argentina
facility: Local Institution - 0100
city: Innsbruck
country: Austria
facility: Local Institution - 0026
state: Tyrol
city: Wels
country: Austria
facility: Local Institution - 0022
state: Upper Austria
city: Fuerstenfeld
country: Austria
facility: Local Institution
city: Graz
country: Austria
facility: Local Institution - 0043
city: Linz
country: Austria
facility: Local Institution - 0024
city: Wien
country: Austria
facility: Local Institution - 0023
city: Brugge
country: Belgium
facility: Local Institution - 0065
city: Merksem
country: Belgium
facility: Local Institution - 0099
city: Yvoir
country: Belgium
facility: Local Institution
city: Goiania
country: Brazil
facility: Local Institution - 0083
state: Goias
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Campinas
country: Brazil
facility: Local Institution - 0063
state: SAO Paulo
city: Ribeirão Preto
country: Brazil
facility: Local Institution
state: SAO Paulo
city: São Paulo
country: Brazil
facility: Local Institution - 0059
state: SAO Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0062
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0058
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0111
city: Saint John
country: Canada
facility: Local Institution - 0020
state: New Brunswick
city: Beijing
country: China
facility: Local Institution - 0071
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0086
state: Beijing
city: Fuzhou
country: China
facility: Local Institution - 0070
state: Fujian
city: Shenzhen
country: China
facility: Local Institution - 0103
state: Guandong
city: Guangzhou
country: China
facility: Local Institution - 0082
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 0074
state: Guangdong
city: Haerbin
country: China
facility: Local Institution - 0084
state: Heilongjiang
city: Wuhan
country: China
facility: Local Institution - 0102
state: Hubei
city: Nanjing
country: China
facility: Local Institution - 0073
state: Jiangsu
city: Suzhou
country: China
facility: Local Institution - 0077
state: Jiangsu
city: Shenyang
country: China
facility: Local Institution - 0094
state: Liaoning
city: Xian
country: China
facility: Local Institution - 0088
state: Shan3xi
city: Jinan
country: China
facility: Local Institution - 0101
state: Shandong
city: Chengdu
country: China
facility: Local Institution - 0075
state: Sichuan
city: Tianjin
country: China
facility: Local Institution - 0069
state: Tianjin
city: Hangzhou
country: China
facility: Local Institution - 0072
city: Shanghai
country: China
facility: Local Institution - 0076
city: Wuhan
country: China
facility: Local Institution - 0096
city: Brno
country: Czechia
facility: Local Institution - 0032
state: Czech Republic
city: Hradec Kralove
country: Czechia
facility: Local Institution
city: Olomouc
country: Czechia
facility: Local Institution
city: Prague 10
country: Czechia
facility: Local Institution
city: Prague 2
country: Czechia
facility: Local Institution - 0067
city: Le Chesnay Cedex
country: France
facility: Local Institution - 0045
city: Lille cedex
country: France
facility: Local Institution - 0041
city: Nantes
country: France
facility: Local Institution
city: Pierre Bénite cedex
country: France
facility: Local Institution
city: Vandoeuvre-les-Nancy Cedex
country: France
facility: Local Institution - 0038
city: Budapest
country: Hungary
facility: Local Institution
city: Szeged
country: Hungary
facility: Local Institution - 0104
city: Brescia
country: Italy
facility: Local Institution - 0106
state: Province Of Brescia
city: Bari
country: Italy
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Catania
country: Italy
facility: Local Institution
city: Firenze
country: Italy
facility: Local Institution - 0027
city: Monza
country: Italy
facility: Local Institution - 0046
city: Napoli
country: Italy
facility: Local Institution
city: Orbassano
country: Italy
facility: Local Institution - 0025
city: Roma
country: Italy
facility: Local Institution - 0021
city: Rome
country: Italy
facility: Local Institution - 0033
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0039
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0050
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0040
city: Krakow
country: Poland
facility: Local Institution - 0048
state: Malopolskie
city: Gdansk
country: Poland
facility: Local Institution - 0047
city: Katowice
country: Poland
facility: Local Institution - 0098
city: Warsaw
country: Poland
facility: Local Institution - 0064
city: A Couruna
country: Spain
facility: Local Institution - 0017
city: L'Hospitalet Del Llobregat
country: Spain
facility: Local Institution - 0018
city: Las Palmas de Gran Canaria
country: Spain
facility: Local Institution - 0015
city: Madrid
country: Spain
facility: Local Institution - 0012
city: Salamanca
country: Spain
facility: Local Institution - 0013
city: Toledo
country: Spain
facility: Local Institution - 0011
city: Muang
country: Thailand
facility: Local Institution - 0055
state: Chiang Mai
city: Bangkok
country: Thailand
facility: Local Institution
city: Khon Kaen
country: Thailand
facility: Local Institution - 0052
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Cortes JE, Jiang Q, Wang J, Weng J, Zhu H, Liu X, Hochhaus A, Kim DW, Radich J, Savona M, Martin-Regueira P, Sy O, Gurnani R, Saglio G. Dasatinib vs. imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) who have not achieved an optimal response to 3 months of imatinib therapy: the DASCERN randomized study. Leukemia. 2020 Aug;34(8):2064-2073. doi: 10.1038/s41375-020-0805-1. Epub 2020 Apr 7.