Open Label, Randomized Phase 2b Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who do Not Have Favorable Imatinib Response (DASCERN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Bristol-Myers Squibb
Sponsor:
Collaborators:
ICON Clinical Research
PPD
Molecular MD
MultiPharma
Quintiles
Donald E. Morisky
MD Anderson Symptom Inventory (MDASI-CML)
OBiS, Inc
Steering Committee
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01593254
First received: May 4, 2012
Last updated: August 18, 2015
Last verified: August 2015
  Purpose

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.


Condition Intervention Phase
Chronic Phase Chronic Myeloid Leukemia
Drug: Imatinib
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of subjects who achieve Major Molecular Response (MMR) rate [ Time Frame: At 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to MMR - Time to MMR is the time between randomization date and first date that MMR criteria are satisfied [ Time Frame: Months 6, 15, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]
  • Time to MR4.5 - Time to Molecular response (MR)4.5 is the time between randomization date and first date that MR4.5 criteria are satisfied [ Time Frame: Months 6, 15, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) - PFS is defined as the time from randomization date to progression date or death date, whichever occurs first. Subjects who neither progress nor die, will be censored [ Time Frame: Months 12, 18, 24, 36, 48 & 60 ] [ Designated as safety issue: No ]
  • Overall Survival (OS)- OS is defined as the time from randomization date to death date. Subjects who have not died, will be censored on the last date they are known to be alive [ Time Frame: Months 12, 18, 24, 36, 48 & 60 ] [ Designated as safety issue: No ]

Estimated Enrollment: 258
Study Start Date: August 2012
Estimated Study Completion Date: January 2022
Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Sprycel

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Chronic Phase (CP)-CML Ph+ patients with CHR but with 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 complete hematologic response (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593254

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 94 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
ICON Clinical Research
PPD
Molecular MD
MultiPharma
Quintiles
Donald E. Morisky
MD Anderson Symptom Inventory (MDASI-CML)
OBiS, Inc
Steering Committee
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01593254     History of Changes
Other Study ID Numbers: CA180-399, 2011-006181-41
Study First Received: May 4, 2012
Last Updated: August 18, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
European Union: European Medicines Agency
Canada: Ethics Review Committee
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Austria: Agency for Health and Food Safety
Argentina: Human Research Bioethics Committee
Austria: Ethikkommission
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Institutional Review Board
Brazil: Ethics Committee
Brazil: National Committee of Ethics in Research
China: Ethics Committee
France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
Italy: Ethics Committee
Poland: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Ethics Committee
Thailand: Ethical Committee
Thailand: Khon Kaen University Ethics Committee for Human Research
Brazil: National Health Surveillance Agency
China: Food and Drug Administration
Czech Republic: Ethics Committee
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Thailand: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Dasatinib
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015