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

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ClinicalTrials.gov Identifier: NCT01593254
Recruitment Status : Active, not recruiting
First Posted : May 8, 2012
Results First Posted : April 11, 2019
Last Update Posted : November 1, 2019
Sponsor:
Collaborators:
ICON Clinical Research
PPD
Molecular MD
MultiPharma
Q2 Solutions
Donald E. Morisky
MD Anderson Symptom Inventory (MDASI-CML)
OBiS, Inc
Steering Committee
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE May 4, 2012
First Posted Date  ICMJE May 8, 2012
Results First Submitted Date  ICMJE November 8, 2018
Results First Posted Date  ICMJE April 11, 2019
Last Update Posted Date November 1, 2019
Actual Study Start Date  ICMJE October 29, 2012
Actual Primary Completion Date November 8, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment [ Time Frame: 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. ]
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). Month 12 is calculated fro
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2012)
Proportion of subjects who achieve Major Molecular Response (MMR) rate [ Time Frame: At 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Median Time to Major Molecular Response (MMR) [ Time Frame: Up to 10 years ]
    Time to MMR is how fast patients achieve optimal response. It is the time between randomization date and first date that MMR criteria are satisfied.
  • Time to Molecular Response (MR)^4.5 [ Time Frame: Up to 10 years ]
    Time to MR^4.5 is how fast patients achieve a deeper response. It is the time between randomization date and first date that MR^4.5 criteria are satisfied.
  • Progression Free Survival (PFS) [ Time Frame: Up to 10 years ]
    PFS is how long patients are likely to live without progression of their disease. It is the time from randomization date to progression date or death date, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Up to 10 years ]
    OS is how long patients are likely to remain alive. It is the time from randomization date to death date.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2012)
  • Molecular Response over time - Proportion of randomized subjects who achieve MMR, MR4 and MR4.5 at each time-point from Day 1 treatment with first line Imatinib [ Time Frame: Months 6, 12, 18, 24, 36, 48 & 60 ]
    MR4 = 4- log reduction in BCR-ABL transcript from the standardized baseline [0.01% International Standard (IS)] MR4.5 = 4.5- log reduction in BCR-ABL transcript from the standardized baseline [0.0032% International Standard (IS)]
  • Cytogenetic Response over time - proportion of randomized subjects who achieve Complete Cytogenetic Response (CCyR) or major cytogenetic response (MCyR) at each time-point from Day 1 treatment with first line Imatinib [ Time Frame: Months 6, 12 & 18 ]
  • 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 ]
  • 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 ]
  • Time to and duration of Response - 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 ]
  • Time to and duration of Response - Time to MR4.5 is the time between randomization date and first date that MR4.5 criteria are satisfied [ Time Frame: Months 6, 12, 15, 18, 24, 36 and 48 ]
  • Time to and duration of Response - Time to MR4 is the time between randomization date and first date that MR4 criteria are satisfied [ Time Frame: Months 6, 12, 15, 18, 24, 36 and 48 ]
  • Time to and duration of Response - Time to CCyR is the time between randomization date and first date that CCyR criteria are satisfied [ Time Frame: Months 6, 12 and 18 ]
  • Time to and duration of Response - Time to MCyR is the time between randomization date and first date that MCyR criteria are satisfied [ Time Frame: Months 6, 12 and 18 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Phase Chronic Myeloid Leukemia
Intervention  ICMJE
  • Drug: Imatinib
    Other Names:
    • Gleevec
    • Glivec
  • Drug: Dasatinib
    Other Name: Sprycel
Study Arms  ICMJE
  • Active Comparator: Arm 1: Imatinib (≥400 mg)
    Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months
    Intervention: Drug: Imatinib
  • Active Comparator: Arm 2: Dasatinib (100 mg)
    Dasatinib 100 mg tablet by mouth QD up to 60 months
    Intervention: Drug: Dasatinib
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
262
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2012)
180
Estimated Study Completion Date  ICMJE February 17, 2022
Actual Primary Completion Date November 8, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Austria,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Hungary,   Italy,   Korea, Republic of,   Poland,   Spain,   Thailand,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01593254
Other Study ID Numbers  ICMJE CA180-399
2011-006181-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE
  • ICON Clinical Research
  • PPD
  • Molecular MD
  • MultiPharma
  • Q2 Solutions
  • Donald E. Morisky
  • MD Anderson Symptom Inventory (MDASI-CML)
  • OBiS, Inc
  • Steering Committee
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP