Chronic Phase Chronic Myeloid Leukemia Clinical Trial
— DASCERNOfficial 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
Verified date | May 2023 |
Source | Bristol-Myers Squibb |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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 |
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 |
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 |
United States, Argentina, Austria, Belgium, Brazil, Canada, China, Czechia, France, Hungary, Italy, Korea, Republic of, Poland, Spain, Thailand,
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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