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

• 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: Bristol-Myers Squibb
• 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: May 4, 2012
• First Posted Date: May 8, 2012
• Results First Submitted Date: November 8, 2018
• Results First Posted Date: April 11, 2019
• Last Update Posted Date: November 1, 2019
• Actual Study Start Date: October 29, 2012
• Actual Primary Completion Date: November 8, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: May 7, 2012): Proportion of subjects who achieve Major Molecular Response (MMR) rate [ Time Frame: At 12 months ]

Current Secondary Outcome Measures (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 (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: Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib
• 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Phase Chronic Myeloid Leukemia

Intervention

• Drug: Imatinib
  Other Names:

  • Gleevec
  • Glivec
• Drug: Dasatinib
  Other Name: Sprycel

Study Arms

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 21, 2019): 262
• Original Estimated Enrollment (submitted: May 7, 2012): 180
• Estimated Study Completion Date: February 17, 2022
• Actual Primary Completion Date: November 8, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT01593254
• Other Study ID Numbers: CA180-399; 2011-006181-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb

Collaborators

• ICON Clinical Research
• PPD
• Molecular MD
• MultiPharma
• Q2 Solutions
• Donald E. Morisky
• MD Anderson Symptom Inventory (MDASI-CML)
• OBiS, Inc
• Steering Committee

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: October 2019