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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Phase Chronic Myeloid Leukemia
• Intervention / Treatment: Drug: Dasatinib; Drug: Imatinib

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 4102-4200
    • Local Institution - 0051
  • Buenos Aires, Argentina, C1114AAN
    • Local Institution - 0057
  • Corrientes, Argentina, CP3400
    • Local Institution - 0100
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina
      • Local Institution - 0093
    • Ramos Mejia, Buenos Aires, Argentina, 1221
      • Local Institution - 0080
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Local Institution - 0049
• Austria
  • Fuerstenfeld, Austria, 8280
    • Local Institution
  • Graz, Austria, 8036
    • Local Institution - 0043
  • Linz, Austria, 4010
    • Local Institution - 0024
  • Wien, Austria, 1090 Wien
    • Local Institution - 0023
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Local Institution - 0026
  • Upper Austria
    • Wels, Upper Austria, Austria, 4600
      • Local Institution - 0022
• Belgium
  • Brugge, Belgium, B-8000
    • Local Institution - 0065
  • Merksem, Belgium, 2170
    • Local Institution - 0099
  • Yvoir, Belgium, 5530
    • Local Institution
• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • Local Institution - 0062
  • Rio de Janeiro, Brazil, 20231-050
    • Local Institution - 0111
  • Rio de Janeiro, Brazil, 20231-050
    • Local Institution - 0058
  • Goias
    • Goiania, Goias, Brazil, 74605-020
      • Local Institution - 0083
  • Parana
    • Curitiba, Parana, Brazil, 80060-900
      • Local Institution
  • SAO Paulo
    • Campinas, SAO Paulo, Brazil, 13083-970
      • Local Institution - 0063
    • Ribeirão Preto, SAO Paulo, Brazil, 14048-900
      • Local Institution
    • São Paulo, SAO Paulo, Brazil, 08270-070
      • Local Institution - 0059
• Canada
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Local Institution - 0020
• China
  • Hangzhou, China, 310003
    • Local Institution - 0072
  • Shanghai, China, 200025
    • Local Institution - 0076
  • Wuhan, China, 430030
    • Local Institution - 0096
  • Beijing
    • Beijing, Beijing, China, 100044
      • Local Institution - 0071
    • Beijing, Beijing, China, 100071
      • Local Institution - 0086
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Local Institution - 0070
  • Guandong
    • Shenzhen, Guandong, China, 518035
      • Local Institution - 0103
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Local Institution - 0082
    • Guangzhou, Guangdong, China, 510515
      • Local Institution - 0074
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150010
      • Local Institution - 0084
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Local Institution - 0102
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Local Institution - 0073
    • Suzhou, Jiangsu, China, 215000
      • Local Institution - 0077
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Local Institution - 0094
  • Shan3xi
    • Xian, Shan3xi, China, 710000
      • Local Institution - 0088
  • Shandong
    • Jinan, Shandong, China, 250012
      • Local Institution - 0101
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0075
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Local Institution - 0069
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Local Institution
  • Olomouc, Czechia, 775 20
    • Local Institution
  • Prague 10, Czechia, 100 34
    • Local Institution
  • Prague 2, Czechia, 12808
    • Local Institution - 0067
  • Czech Republic
    • Brno, Czech Republic, Czechia, 625 00
      • Local Institution - 0032
• France
  • Le Chesnay Cedex, France, 78157
    • Local Institution - 0045
  • Lille cedex, France, 59037
    • Local Institution - 0041
  • Nantes, France, 44000
    • Local Institution
  • Pierre Bénite cedex, France, 69495
    • Local Institution
  • Vandoeuvre-les-Nancy Cedex, France, 54511
    • Local Institution - 0038
• Hungary
  • Budapest, Hungary, 1083
    • Local Institution
  • Szeged, Hungary, 6725
    • Local Institution - 0104
• Italy
  • Bari, Italy, 70124
    • Local Institution
  • Bologna, Italy, 40138
    • Local Institution
  • Catania, Italy, 95124
    • Local Institution
  • Firenze, Italy, 50134
    • Local Institution - 0027
  • Monza, Italy, 20900
    • Local Institution - 0046
  • Napoli, Italy, 80131
    • Local Institution
  • Orbassano, Italy, 10143
    • Local Institution - 0025
  • Roma, Italy, 00144
    • Local Institution - 0021
  • Rome, Italy, 00161
    • Local Institution - 0033
  • Province Of Brescia
    • Brescia, Province Of Brescia, Italy, 25123
      • Local Institution - 0106
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Local Institution - 0039
  • Seoul, Korea, Republic of, 137-701
    • Local Institution - 0050
  • Seoul, Korea, Republic of, 138-736
    • Local Institution - 0040
• Poland
  • Gdansk, Poland, 80-952
    • Local Institution - 0047
  • Katowice, Poland, 40-032
    • Local Institution - 0098
  • Warsaw, Poland, 02-776
    • Local Institution - 0064
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Local Institution - 0048
• Spain
  • A Couruna, Spain, 15706
    • Local Institution - 0017
  • L'Hospitalet Del Llobregat, Spain, 08908
    • Local Institution - 0018
  • Las Palmas de Gran Canaria, Spain, 35010
    • Local Institution - 0015
  • Madrid, Spain, 28007
    • Local Institution - 0012
  • Salamanca, Spain, 37007
    • Local Institution - 0013
  • Toledo, Spain, 45004
    • Local Institution - 0011
• Thailand
  • Bangkok, Thailand, 10400
    • Local Institution
  • Khon Kaen, Thailand, 40002
    • Local Institution - 0052
  • Chiang Mai
    • Muang, Chiang Mai, Thailand, 50200
      • Local Institution - 0055
• United States
  • California
    • Anaheim, California, United States, 92801
      • Local Institution - 0004
    • Fontana, California, United States, 92335
      • Local Institution - 0006
    • Los Angeles, California, United States, 90033
      • University of Southern California University Hospital
    • Roseville, California, United States, 95661
      • Local Institution - 0110
    • San Jose, California, United States, 95119
      • Local Institution - 0112
    • Vallejo, California, United States, 94589-2441
      • Local Institution - 0009
    • Whittier, California, United States, 90603
      • Local Institution - 0078
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • Local Institution - 0089
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Crown Point, Indiana, United States, 46307
      • Northern Indiana Cancer Research Consortium
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0010
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Local Institution - 0002
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1625
      • Local Institution - 0001
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E DeBakey VAMC
    • Laredo, Texas, United States, 78041
      • Institute of Oncology Hematology Biomedical Research
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Local Institution - 0005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Imatinib (≥400 mg); Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months	Drug: Imatinib; Other Names: Gleevec; Glivec
Active Comparator: Arm 2: Dasatinib (100 mg); Dasatinib 100 mg tablet by mouth QD up to 60 months	Drug: Dasatinib; Other Names: Sprycel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: PPD; ICON Clinical Research; Q2 Solutions; Molecular MD; MultiPharma; Steering Committee; Donald E. Morisky; MD Anderson Symptom Inventory (MDASI-CML); OBiS, Inc
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2012
• Primary Completion (Actual): November 8, 2017
• Study Completion (Actual): April 12, 2022

Study Registration Dates

• First Submitted: May 4, 2012
• First Submitted That Met QC Criteria: May 7, 2012
• First Posted (Estimated): May 8, 2012

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate; Dasatinib
• Other Study ID Numbers: CA180-399; 2011-006181-41 (EudraCT Number)