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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2

Conditions: Chronic Phase Chronic Myeloid Leukemia

Treatments: Drug: Imatinib; Drug: Dasatinib

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT01593254

CA180-399

2011-006181-41 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 262 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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262 participants in 2 patient groups

Arm 1: Imatinib (≥400 mg)

Active Comparator group

Description:

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

Treatment:

Drug: Imatinib

Arm 2: Dasatinib (100 mg)

Active Comparator group

Description:

Dasatinib 100 mg tablet by mouth QD up to 60 months

Treatment:

Drug: Dasatinib