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

NCT01593254 | Completed Phase 2 Results DMC

• 2 other identifiers: CA180-3992011-006181-41
• Study Type: interventional
• Target: 262
• Locations: 15 countries
• Sites: 101

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.

Conditions

Chronic Phase Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Median Time to Major Molecular Response (MMR)

  From randomization to study completion. Approximately 115 months

• Time to Molecular Response (MR)^4.5

  From randomization to study completion. Approximately 115 months

• Progression Free Survival (PFS)

  From randomization to study completion. Approximately 115 months

• Overall Survival (OS)

  From randomization to study completion. Approximately 115 months

Study Arms (2)

Arm 1: Imatinib (≥400 mg)

ACTIVE COMPARATOR

Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months

Drug: Imatinib

Arm 2: Dasatinib (100 mg)

ACTIVE COMPARATOR

Dasatinib 100 mg tablet by mouth QD up to 60 months

Drug: Dasatinib

Interventions

Imatinib DRUG

Also known as: Gleevec, Glivec

Arm 1: Imatinib (≥400 mg)

Dasatinib DRUG

Also known as: Sprycel

Arm 2: Dasatinib (100 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• ICON Clinical Research: collaborator
• PPD Development, LP: collaborator
• Molecular MD: collaborator
• MultiPharma: collaborator
• Q2 Solutions: collaborator
• Donald E. Morisky: collaborator
• MD Anderson Symptom Inventory (MDASI-CML): collaborator
• OBiS, Inc: collaborator
• Steering Committee: collaborator

Study Sites (101)

Local Institution - 0004

Anaheim, California, 92801, United States

Location

Local Institution - 0006

Fontana, California, 92335, United States

Location

University Of Southern California University Hospital

Los Angeles, California, 90033, United States

Location

Local Institution - 0110

Roseville, California, 95661, United States

Location

Local Institution - 0112

San Jose, California, 95119, United States

Location

Local Institution - 0009

Vallejo, California, 94589-2441, United States

Location

Local Institution - 0078

Whittier, California, 90603, United States

Location

Local Institution - 0089

Southington, Connecticut, 06489, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Northern Indiana Cancer Research Consortium

Crown Point, Indiana, 46307, United States

Location

Franciscan St. Francis Health

Indianapolis, Indiana, 46237, United States

Location

University Of Iowa

Iowa City, Iowa, 52242, United States

Location

Local Institution - 0010

Rochester, Minnesota, 55905, United States

Location

Local Institution - 0002

Cincinnati, Ohio, 45242, United States

Location

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 0001

Nashville, Tennessee, 37203-1625, United States

Location

Michael E Debakey VAMC

Houston, Texas, 77030, United States

Location

Institute of Oncology Hematology Biomedical Research

Laredo, Texas, 78041, United States

Location

Edwards Comprehensive Cancer Center

Huntington, West Virginia, 25701, United States

Location

Local Institution - 0005

Milwaukee, Wisconsin, 53226, United States

Location

Local Institution - 0093

La Plata, Buenos Aires, 0, Argentina

Location

Local Institution - 0080

Ramos Mejía, Buenos Aires, 1221, Argentina

Location

Local Institution - 0049

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Local Institution - 0051

Buenos Aires, 4102-4200, Argentina

Location

Local Institution - 0057

Buenos Aires, C1114AAN, Argentina

Location

Local Institution - 0100

Corrientes, CP3400, Argentina

Location

Local Institution - 0026

Innsbruck, Tyrol, 6020, Austria

Location

Local Institution - 0022

Wels, Upper Austria, 4600, Austria

Location

Local Institution

Fürstenfeld, 8280, Austria

Location

Local Institution - 0043

Graz, 8036, Austria

Location

Local Institution - 0024

Linz, 4010, Austria

Location

Local Institution - 0023

Vienna, 1090 Wien, Austria

Location

Local Institution - 0065

Bruges, B-8000, Belgium

Location

Local Institution - 0099

Merksem, 2170, Belgium

Location

Local Institution

Yvoir, 5530, Belgium

Location

Local Institution - 0083

Goiânia, Goiás, 74605-020, Brazil

Location

Local Institution

Curitiba, Paraná, 80060-900, Brazil

Location

Local Institution - 0063

Campinas, São Paulo, 13083-970, Brazil

Location

Local Institution

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Local Institution - 0059

São Paulo, São Paulo, 08270-070, Brazil

Location

Local Institution - 0062

Rio de Janeiro, 20211-030, Brazil

Location

Local Institution - 0058

Rio de Janeiro, 20231-050, Brazil

Location

Local Institution - 0111

Rio de Janeiro, 20231-050, Brazil

Location

Local Institution - 0020

Saint John, New Brunswick, E2L 4L2, Canada

Location

Local Institution - 0071

Beijing, Beijing Municipality, 100044, China

Location

Local Institution - 0086

Beijing, Beijing Municipality, 100071, China

Location

Local Institution - 0070

Fuzhou, Fujian, 350001, China

Location

Local Institution - 0103

Shenzhen, Guandong, 518035, China

Location

Local Institution - 0082

Guangzhou, Guangdong, 510080, China

Location

Local Institution - 0074

Guangzhou, Guangdong, 510515, China

Location

Local Institution - 0084

Haerbin, Heilongjiang, 150010, China

Location

Local Institution - 0102

Wuhan, Hubei, 430030, China

Location

Local Institution - 0073

Nanjing, Jiangsu, 210029, China

Location

Local Institution - 0077

Suzhou, Jiangsu, 215000, China

Location

Local Institution - 0094

Shenyang, Liaoning, 110001, China

Location

Local Institution - 0088

Xi'an, Shan3xi, 710000, China

Location

Local Institution - 0101

Jinan, Shandong, 250012, China

Location

Local Institution - 0075

Chengdu, Sichuan, 610041, China

Location

Local Institution - 0069

Tianjin, Tianjin Municipality, 300020, China

Location

Local Institution - 0072

Hangzhou, 310003, China

Location

Local Institution - 0076

Shanghai, 200025, China

Location

Local Institution - 0096

Wuhan, 430030, China

Location

Local Institution - 0032

Brno, Czech Republic, 625 00, Czechia

Location

Local Institution

Hradec Králové, 500 05, Czechia

Location

Local Institution

Olomouc, 775 20, Czechia

Location

Local Institution

Prague, 100 34, Czechia

Location

Local Institution - 0067

Prague, 12808, Czechia

Location

Local Institution - 0045

Le Chesnay, 78157, France

Location

Local Institution - 0041

Lille, 59037, France

Location

Local Institution

Nantes, 44000, France

Location

Local Institution

Pierre-Bénite, 69495, France

Location

Local Institution - 0038

Vandœuvre-lès-Nancy, 54511, France

Location

Local Institution

Budapest, 1083, Hungary

Location

Local Institution - 0104

Szeged, 6725, Hungary

Location

Local Institution - 0106

Brescia, Province Of Brescia, 25123, Italy

Location

Local Institution

Bari, 70124, Italy

Location

Local Institution

Bologna, 40138, Italy

Location

Local Institution

Catania, 95124, Italy

Location

Local Institution - 0027

Florence, 50134, Italy

Location

Local Institution - 0046

Monza, 20900, Italy

Location

Local Institution

Napoli, 80131, Italy

Location

Local Institution - 0025

Orbassano, 10143, Italy

Location

Local Institution - 0021

Roma, 00144, Italy

Location

Local Institution - 0033

Rome, 00161, Italy

Location

Local Institution - 0048

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

Local Institution - 0047

Gdansk, 80-952, Poland

Location

Local Institution - 0098

Katowice, 40-032, Poland

Location

Local Institution - 0064

Warsaw, 02-776, Poland

Location

Local Institution - 0039

Seoul, 06351, South Korea

Location

Local Institution - 0050

Seoul, 137-701, South Korea

Location

Local Institution - 0040

Seoul, 138-736, South Korea

Location

Local Institution - 0017

A Couruna, 15706, Spain

Location

Local Institution - 0018

L'Hospitalet Del Llobregat, 08908, Spain

Location

Local Institution - 0015

Las Palmas de Gran Canaria, 35010, Spain

Location

Local Institution - 0012

Madrid, 28007, Spain

Location

Local Institution - 0013

Salamanca, 37007, Spain

Location

Local Institution - 0011

Toledo, 45004, Spain

Location

Local Institution - 0055

Muang, Chiang Mai, 50200, Thailand

Location

Local Institution

Bangkok, 10400, Thailand

Location

Local Institution - 0052

Khon Kaen, 40002, Thailand

Location

Related Publications (1)

• 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.

  PMID: 32265500 DERIVED

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

Imatinib Mesylate; Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2012
• First Posted: May 8, 2012
• Study Start: September 12, 2012
• Primary Completion: November 8, 2017
• Study Completion: April 12, 2022
• Last Updated: June 22, 2023
• Results First Posted: April 11, 2019

Record last verified: 2023-05

Locations

CA (1); US (21); CZ (5); HU (2); KR (3); IT (10); AU (6); TH (3); AR (6); BR (8); PL (4); CN (18); BE (3); FR (5); ES (6)