Randomized Study Comparing the Effect of Dasatinib and Imatinib on Malignant Stem Cells in Chronic Myeloid Leukemia (NordCML006)
A randomized multi-center study comparing the effect of dasatinib and imatinib on malignant stem cells in newly diagnosed chronic phase chronic myeloid leukemia (CML) patients. The research hypothesis is that 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 CML patients. The study duration is 18 months and approximately 40 patients will be recruited to the study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Ph-positive cells in stem cell compartments [ Time Frame: 6 months ] [ Designated as safety issue: No ]proportion of Ph-positive cells in stem cell compartments (CD34+CD38neg and CD34+CD38+)
- BCR-ABL RQ-PCR in blood [ Time Frame: up to 18 months (1, 3, 6, 12 and 18 months) ] [ Designated as safety issue: No ]
|Study Start Date:||March 2009|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Active Comparator: Imatinib
Standard treatment Imatinib 400mg OD
Per oral imatinib 400mg once daily (continuous medication)
Other Name: Glivec
Dasatinib 100mg OD
Per oral dasatinib 100mg once daily (continuous medication)
Other Name: Sprycel
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 and Stockholm).
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) patients.
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 flow cytometer.
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.
|Helsinki University Central Hospital|
|Helsinki, Finland, 00029|
|Bergen University Central Hospital|
|Oslo, Norway, 0027|
|St. Olavs Hospital|
|Trondheim, Norway, 7006|
|Lund University Hospital|
|Lund, Sweden, 22185|
|Karolinska University Hospital|
|Stockholm, Sweden, 17176|
|Uppsala University Hospital|
|Uppsala, Sweden, 75185|
|Principal Investigator:||Satu Mustjoki, MD, PhD||Helsinki University Central Hospital, helsinki, Finland|
|Study Chair:||Henrik Hjorth-Hansen, MD, PhD||St Olavs Hospital, Trondheim, Norway|
|Study Chair:||Ole Weiss-Bjerrum, MD, PhD||Rigshospitalet, Denmark|
|Study Chair:||Ingunn Dybedal, MD, PhD||Rikshospitalet, Oslo, Norway|
|Study Chair:||Tobias Gedde-Dahl, MD, PhD||Rikshospitalet, Oslo, Norway|
|Study Chair:||Kimmo Porkka, MD, PhD||Helsinki University Central Hospital, Helsinki, Finland|
|Study Chair:||Johan Richter, MD, PhD||University of Lund, Lund, Sweden|
|Study Chair:||Bengt Simonsson, MD, PhD||University Hospital, Uppsala, Sweden|
|Study Chair:||Leif Stenke, MD, PhD||Karolinska Institutet|