Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib

Phase 2

Completed

Conditions: Chronic Phase Chronic Myeloid Leukemia

Interventions: Drug: Imatinib
Drug: Dasatinib

Registration Number: NCT01593254

Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 262

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Imatinib (≥400 mg)	Imatinib	Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months
Arm 2: Dasatinib (100 mg)	Dasatinib	Dasatinib 100 mg tablet by mouth QD up to 60 months

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment	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.	Major Molecular Response, is defined as a 3-log reduction in BCR-ABL transcripts from the standardized baseline, which represents 100% on the international scale, so a 3-log reduction is fixed at 0.1% for MMR; N/A = not applicable. 95% CI is Clopper-Pearson(Exact) two-sided 95% confidence intervals. P-value is based on Cochran-Mantel-Haenszel (CMH) test stratified by Sokal score(high, intermediate, low, and unknown) and time between 3 month molecular analysis and randomization (\<=4 weeks vs \>4 weeks).

Secondary Outcome Measures

Name	Time	Method
Median Time to Major Molecular Response (MMR)	From randomization to study completion. Approximately 115 months	Median Time to Major Molecular Response (MMR) is the time between randomization date and first date that MMR (or MR4.5) criteria are satisfied. Participants who do not achieve MMR (or MR4.5) will be censored. Major Molecular Response, is defined as a 3-log reduction in BCR-ABL transcripts from the standardized baseline, which represents 100% on the international scale, so a 3-log reduction is fixed at 0.1% for MMR.
Time to Molecular Response (MR)^4.5	From randomization to study completion. Approximately 115 months	Time to Molecular Response (MR)\^4.5 is the time between randomization date and first date that MMR (or MR4.5) criteria are satisfied. Participants who do not achieve MMR (or MR4.5) will be censored. MR4.5 is defined as a 4.5-log reduction in BCR-ABL transcript from the standardized baseline (0.0032% IS, either detectable disease \<= 0.0032% BCR-ABL (IS) or undetectable disease in cDNA (in same volume used for BCR-ABL) with \>= 32,000 ABL transcripts.
Progression Free Survival (PFS)	From randomization to study completion. Approximately 115 months	PFS is the time from randomization date to progression date or death date, whichever occurs first. Participants who neither progress nor die will be censored. Progression is defined as the following, meeting the criteria for accelerated or blast crisis CML are met at any time or death from any cause during treatment. Accelerated phase of CML: * The presence of ≥15%, but \< 30% blasts in the blood or bone marrow * At least 30% blasts plus promyelocytes in the blood or bone marrow * At least 20% peripheral basophils * Thrombocytopenia (fewer than 100,000 platelets/mm3) unrelated to treatment. Blast phase of CML * At least 30% blasts in the blood or bone marrow * Extramedullary involvement (e.g., chloromas), but not hepatosplenomegaly
Overall Survival (OS)	From randomization to study completion. Approximately 115 months	OS is the time from randomization date to death date. Participants who have not died will be censored on the last date they are known to be alive.

Trial Locations

Locations (87): Northern Indiana Cancer Research Consortium
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Crown Point, Indiana, United States
Local Institution - 0006
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Fontana, California, United States
Local Institution - 0021
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Roma, Italy
Local Institution - 0027
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Firenze, Italy
Local Institution - 0047
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Gdansk, Poland
Local Institution - 0064
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Warsaw, Poland
Local Institution - 0018
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L'Hospitalet Del Llobregat, Spain
Local Institution - 0012
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Madrid, Spain
Local Institution - 0098
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Katowice, Poland
Local Institution - 0055
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Muang, Chiang Mai, Thailand
Local Institution - 0046
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Monza, Italy
Local Institution - 0033
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Rome, Italy
Local Institution - 0040
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Seoul, Korea, Republic of
Local Institution - 0025
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Orbassano, Italy
Local Institution - 0013
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Salamanca, Spain
Local Institution - 0017
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A Couruna, Spain
Local Institution - 0015
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Las Palmas de Gran Canaria, Spain
Local Institution - 0048
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Krakow, Malopolskie, Poland
Local Institution - 0011
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Toledo, Spain
Local Institution - 0106
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Brescia, Province Of Brescia, Italy
Local Institution - 0026
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Innsbruck, Tyrol, Austria
Local Institution
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Bangkok, Thailand
Local Institution - 0004
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Anaheim, California, United States
University Of Southern California University Hospital
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Los Angeles, California, United States
Local Institution - 0009
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Vallejo, California, United States
Northwestern University
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Evanston, Illinois, United States
Carle Cancer Center
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Urbana, Illinois, United States
Local Institution - 0020
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Saint John, New Brunswick, Canada
Franciscan St. Francis Health
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Indianapolis, Indiana, United States
Local Institution - 0002
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Cincinnati, Ohio, United States
Michael E Debakey VAMC
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Houston, Texas, United States
Local Institution - 0082
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Guangzhou, Guangdong, China
Local Institution - 0103
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Shenzhen, Guandong, China
Local Institution - 0084
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Haerbin, Heilongjiang, China
Local Institution - 0102
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Wuhan, Hubei, China
Local Institution - 0073
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Nanjing, Jiangsu, China
Local Institution - 0094
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Shenyang, Liaoning, China
Local Institution - 0088
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Xian, Shan3xi, China
Local Institution - 0075
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Chengdu, Sichuan, China
Local Institution - 0069
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Tianjin, Tianjin, China
Local Institution - 0072
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Hangzhou, China
Local Institution - 0096
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Wuhan, China
Local Institution - 0110
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Roseville, California, United States
Local Institution - 0112
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San Jose, California, United States
Local Institution - 0078
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Whittier, California, United States
Local Institution - 0089
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Southington, Connecticut, United States
University Of Iowa
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Iowa City, Iowa, United States
Hillman Cancer Center
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Pittsburgh, Pennsylvania, United States
Edwards Comprehensive Cancer Center
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Huntington, West Virginia, United States
Institute of Oncology Hematology Biomedical Research
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Laredo, Texas, United States
Local Institution - 0049
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San Miguel de Tucuman, Tucuman, Argentina
Local Institution - 0057
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Buenos Aires, Argentina
Local Institution - 0093
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La Plata, Buenos Aires, Argentina
Local Institution - 0051
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Buenos Aires, Argentina
Local Institution - 0080
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Ramos Mejia, Buenos Aires, Argentina
Local Institution - 0022
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Wels, Upper Austria, Austria
Local Institution - 0100
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Corrientes, Argentina
Local Institution - 0023
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Wien, Austria
Local Institution - 0065
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Brugge, Belgium
Local Institution - 0099
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Merksem, Belgium
Local Institution - 0058
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Rio de Janeiro, Brazil
Local Institution - 0083
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Goiania, Goias, Brazil
Local Institution - 0062
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Rio de Janeiro, Brazil
Local Institution - 0059
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São Paulo, SAO Paulo, Brazil
Local Institution - 0063
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Campinas, SAO Paulo, Brazil
Local Institution - 0111
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Rio de Janeiro, Brazil
Local Institution - 0071
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Beijing, Beijing, China
Local Institution - 0086
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Beijing, Beijing, China
Local Institution - 0070
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Fuzhou, Fujian, China
Local Institution - 0074
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Guangzhou, Guangdong, China
Local Institution - 0077
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Suzhou, Jiangsu, China
Local Institution - 0101
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Jinan, Shandong, China
Local Institution - 0076
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Shanghai, China
Local Institution - 0032
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Brno, Czech Republic, Czechia
Local Institution - 0038
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Vandoeuvre-les-Nancy Cedex, France
Local Institution - 0045
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Le Chesnay Cedex, France
Local Institution - 0041
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Lille cedex, France
Local Institution - 0067
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Prague 2, Czechia
Local Institution - 0104
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Szeged, Hungary
Local Institution - 0050
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Seoul, Korea, Republic of
Local Institution - 0039
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Seoul, Korea, Republic of
Local Institution - 0024
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Linz, Austria
Local Institution - 0043
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Graz, Austria
Local Institution - 0052
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Khon Kaen, Thailand
Local Institution - 0010
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Rochester, Minnesota, United States
Local Institution - 0001
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Nashville, Tennessee, United States
Local Institution - 0005
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Milwaukee, Wisconsin, United States