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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01593254
Other study ID # CA180-399
Secondary ID 2011-006181-41
Status Completed
Phase Phase 2
First received
Last updated
Start date September 12, 2012
Est. completion date April 12, 2022

Study information

Verified date May 2023
Source Bristol-Myers Squibb
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 262
Est. completion date April 12, 2022
Est. primary completion date November 8, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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


Related Conditions & MeSH terms


Intervention

Drug:
Imatinib

Dasatinib


Locations

Country Name City State
Argentina Local Institution - 0051 Buenos Aires
Argentina Local Institution - 0057 Buenos Aires
Argentina Local Institution - 0100 Corrientes
Argentina Local Institution - 0093 La Plata Buenos Aires
Argentina Local Institution - 0080 Ramos Mejia Buenos Aires
Argentina Local Institution - 0049 San Miguel de Tucuman Tucuman
Austria Local Institution Fuerstenfeld
Austria Local Institution - 0043 Graz
Austria Local Institution - 0026 Innsbruck Tyrol
Austria Local Institution - 0024 Linz
Austria Local Institution - 0022 Wels Upper Austria
Austria Local Institution - 0023 Wien
Belgium Local Institution - 0065 Brugge
Belgium Local Institution - 0099 Merksem
Belgium Local Institution Yvoir
Brazil Local Institution - 0063 Campinas SAO Paulo
Brazil Local Institution Curitiba Parana
Brazil Local Institution - 0083 Goiania Goias
Brazil Local Institution Ribeirão Preto SAO Paulo
Brazil Local Institution - 0058 Rio de Janeiro
Brazil Local Institution - 0062 Rio de Janeiro
Brazil Local Institution - 0111 Rio de Janeiro
Brazil Local Institution - 0059 São Paulo SAO Paulo
Canada Local Institution - 0020 Saint John New Brunswick
China Local Institution - 0071 Beijing Beijing
China Local Institution - 0086 Beijing Beijing
China Local Institution - 0075 Chengdu Sichuan
China Local Institution - 0070 Fuzhou Fujian
China Local Institution - 0074 Guangzhou Guangdong
China Local Institution - 0082 Guangzhou Guangdong
China Local Institution - 0084 Haerbin Heilongjiang
China Local Institution - 0072 Hangzhou
China Local Institution - 0101 Jinan Shandong
China Local Institution - 0073 Nanjing Jiangsu
China Local Institution - 0076 Shanghai
China Local Institution - 0094 Shenyang Liaoning
China Local Institution - 0103 Shenzhen Guandong
China Local Institution - 0077 Suzhou Jiangsu
China Local Institution - 0069 Tianjin Tianjin
China Local Institution - 0096 Wuhan
China Local Institution - 0102 Wuhan Hubei
China Local Institution - 0088 Xian Shan3xi
Czechia Local Institution - 0032 Brno Czech Republic
Czechia Local Institution Hradec Kralove
Czechia Local Institution Olomouc
Czechia Local Institution Prague 10
Czechia Local Institution - 0067 Prague 2
France Local Institution - 0045 Le Chesnay Cedex
France Local Institution - 0041 Lille cedex
France Local Institution Nantes
France Local Institution Pierre Bénite cedex
France Local Institution - 0038 Vandoeuvre-les-Nancy Cedex
Hungary Local Institution Budapest
Hungary Local Institution - 0104 Szeged
Italy Local Institution Bari
Italy Local Institution Bologna
Italy Local Institution - 0106 Brescia Province Of Brescia
Italy Local Institution Catania
Italy Local Institution - 0027 Firenze
Italy Local Institution - 0046 Monza
Italy Local Institution Napoli
Italy Local Institution - 0025 Orbassano
Italy Local Institution - 0021 Roma
Italy Local Institution - 0033 Rome
Korea, Republic of Local Institution - 0039 Seoul
Korea, Republic of Local Institution - 0040 Seoul
Korea, Republic of Local Institution - 0050 Seoul
Poland Local Institution - 0047 Gdansk
Poland Local Institution - 0098 Katowice
Poland Local Institution - 0048 Krakow Malopolskie
Poland Local Institution - 0064 Warsaw
Spain Local Institution - 0017 A Couruna
Spain Local Institution - 0018 L'Hospitalet Del Llobregat
Spain Local Institution - 0015 Las Palmas de Gran Canaria
Spain Local Institution - 0012 Madrid
Spain Local Institution - 0013 Salamanca
Spain Local Institution - 0011 Toledo
Thailand Local Institution Bangkok
Thailand Local Institution - 0052 Khon Kaen
Thailand Local Institution - 0055 Muang Chiang Mai
United States Local Institution - 0004 Anaheim California
United States Local Institution - 0002 Cincinnati Ohio
United States Northern Indiana Cancer Research Consortium Crown Point Indiana
United States Northwestern University Evanston Illinois
United States Local Institution - 0006 Fontana California
United States Michael E Debakey VAMC Houston Texas
United States Edwards Comprehensive Cancer Center Huntington West Virginia
United States Franciscan St. Francis Health Indianapolis Indiana
United States University Of Iowa Iowa City Iowa
United States Institute of Oncology Hematology Biomedical Research Laredo Texas
United States University Of Southern California University Hospital Los Angeles California
United States Local Institution - 0005 Milwaukee Wisconsin
United States Local Institution - 0001 Nashville Tennessee
United States Hillman Cancer Center Pittsburgh Pennsylvania
United States Local Institution - 0010 Rochester Minnesota
United States Local Institution - 0110 Roseville California
United States Local Institution - 0112 San Jose California
United States Local Institution - 0089 Southington Connecticut
United States Carle Cancer Center Urbana Illinois
United States Local Institution - 0009 Vallejo California
United States Local Institution - 0078 Whittier California

Sponsors (10)

Lead Sponsor Collaborator
Bristol-Myers Squibb Donald E. Morisky, ICON Clinical Research, MD Anderson Symptom Inventory (MDASI-CML), Molecular MD, MultiPharma, OBiS, Inc, PPD, Q2 Solutions, Steering Committee

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Hungary,  Italy,  Korea, Republic of,  Poland,  Spain,  Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment 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).
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 Median Time to Major Molecular Response (MMR) 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.
From randomization to study completion. Approximately 115 months
Secondary Time to Molecular Response (MR)^4.5 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.
From randomization to study completion. Approximately 115 months
Secondary Progression Free Survival (PFS) 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
From randomization to study completion. Approximately 115 months
Secondary Overall Survival (OS) 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. From randomization to study completion. Approximately 115 months
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