An Open-Label, Randomized, Multicenter Phase II Trial Comparing the Depletion of Malignant Stem Cells With Dasatinib vs. Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid
An Open-Label, Randomized, Multicenter Phase II Trial Comparing the depletion of malignant
stem cells with Dasatinib vs. Imatinib in Patients with Newly Diagnosed Chronic Phase
Chronic Myeloid Leukemia
Estimated Number of Study Centers and Countries/Regions: Appr. 12 sites in 5 Nordic
countries. Stem cell analyses will be performed in 4 Nordic centers (Helsinki, Lund, Oslo
Study Phase: II
Research Hypothesis: Treatment with dasatinib 100 mg daily (QD) results in greater and more
rapid depletion of the Philadelphia (Ph) -positive stem cell pool within 6 months of therapy
than imatinib 400 mg QD in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML)
Primary Objective: To compare the number of Ph-positive cells in the stem cell compartment
in newly diagnosed CP CML patients treated with dasatinib 100 mg QD vs. imatinib 400 mg QD.
Study Design: open-label randomized Phase II trial in newly diagnosed CML patients in CP.
Patients will be randomized to receive dasatinib at a starting dose of 100 mg QD or imatinib
at a starting dose of 400 mg QD.
Duration of Study: The study will be open for enrollment until the planned number of 40
patients is randomized. All patients will be treated and/or followed for up to 18 months.
Based on the amendment 1 (Oct 2011), the follow-up of the patients will continue additional
4 years until 31.12.2015.
Number of Patients per Group: Approximately 40 patients will be randomized, 20 patients to
dasatinib and 20 to imatinib. Additional patients will be recruited in case insufficient
amount of representative samples have been obtained from first 40 patients.
Study Population: Patients 18 years or older with a newly diagnosed CP CML, not previously
treated with any systemic treatments for CML
Study Assessments and Endpoints:
All stem cell assays are based on the preselection of CD34+ cells from large volume of bone
marrow (BM) aspirates using paramagnetic beads. The CD34+ fraction will be further
subdivided based on the expression of CD38 marker (positive vs. negative) using a sorting
The primary endpoint is a comparison of proportion of Ph-positive cells in stem cell
compartments (CD34+CD38neg and CD34+CD38+) at 6 months between the study arms.
Secondary endpoints are comparisons between treatment arms for: (1) the number of
Ph-positive cells in all stem cell compartments at 1 and 3 months, (2) BCR-ABL RQ-PCR in
blood at 1, 3, 6, 12 and 18 months, and (3) rate of CCyR within 3, 6, 12 and 18 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Ph-positive cells in stem cell compartments
proportion of Ph-positive cells in stem cell compartments (CD34+CD38neg and CD34+CD38+)
Satu Mustjoki, MD, PhD
Helsinki University Central Hospital, helsinki, Finland
Finland: Finnish Medicines Agency