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

Chronic Phase Chronic Myeloid Leukemia Clinical Trial

— DASCERN  

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

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
• 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
• 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

Related Conditions & MeSH terms

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

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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls