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Randomized Study Comparing the Effect of Dasatinib and Imatinib on Malignant Stem Cells in Chronic Myeloid Leukemia
Link to the ClinicalTrials.gov recordInformation obtained from ClinicalTrials.gov on February 23, 2012
Title of trial/grant titleRandomized Study Comparing the Effect of Dasatinib and Imatinib on Malignant Stem Cells in Chronic Myeloid Leukemia
Current status of trialActive, not recruiting
Sponsors and collaboratorsNorwegian University of Science and Technology
Information provided byNorwegian University of Science and Technology
ClinicalTrials.gov identifierNCT00852566
PurposeA 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.
Condition(s)Chronic Myeloid Leukemia
Intervention(s)Drug: Imatinib
Drug: Dasatinib
PhasePhase II
Study type and designAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Official titleAn 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
Further study detailsAn 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.
Primary outcomePh-positive cells in stem cell compartments 6 months No proportion of Ph-positive cells in stem cell compartments (CD34+CD38neg and CD34+CD38+)
Secondary outcomeBCR-ABL RQ-PCR in blood up to 18 months (1, 3, 6, 12 and 18 months) No
Study startMarch 2009
Minimum age18 Years
Maximum ageN/A
GenderBoth
Eligibility criteriaInclusion Criteria:

- Patients are able to provide written informed consent

- Patients must have CML in CP which is defined by the presence of all of the following
criteria:

- < 15% blasts in peripheral blood (PB) and BM.

- < 30% blasts plus promyelocytes in PB and BM.

- < 20% basophils in the PB.

- â¿¥ 100 x 109/L platelets.

- No evidence of extramedullary leukemia apart from hepatosplenomegaly

- Ph+ or variants must be demonstrated by BM cytogenetics, FISH or PCR.

- Previously untreated CML in CP, with the exception of hydroxyurea or anagrelide

- Patients must be enrolled in this study within 90 days after the date of first being
diagnosed with CML

- ECOG Performance Status (PS) Score 0 - 1 (see Appendix 2)

- Adequate hepatic function defined as: total bilirubin ⿤ 2.0 times the institutional
upper limit of normal (ULN) in absence of Gilbert type unconjugated
hyperbilirubinemia; alanine aminotransferase (ALAT⿤ 2.5 times the institutional ULN.

- Adequate renal function defined as serum creatinine ⿤ 2 times the institutional ULN.

- Men and women, ages 18 years and older.

- Adequate BM aspiration sample before the start of study treatment (i.e sample is
sufficient for stem cell analysis)

- Potentially fertile women must use an adequate method of contraception to avoid
pregnancy throughout the study.

- Potentially fertile women must have a negative serum or urine pregnancy test

Exclusion Criteria:

- Fertile women who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study

- Women who are pregnant or breastfeeding.

- Men with fertile sexual partners who can or will not use an acceptable contraception
method for the entire study

- A serious uncontrolled medical disorder or active infection that would impair the
ability of the subject to receive protocol therapy.

- Known pleural effusion at baseline.

- Uncontrolled or significant cardiovascular disease

- History of significant bleeding disorder unrelated to CML, including:

- Prior chemotherapy for peripheral stem cell mobilization.

- Inadequate BM aspiration sample due to marrow fibrosis or other reasons

- Prior or concurrent malignancy

- Severe psychiatric illness, imprisonment or mental impairment inflicting on ability
to give informed consent

- Abuse of alcohol, prescribed or illicit drugs

- Evidence of digestive dysfunction that would prevent administration of study therapy
by mouth.

- Prohibited Treatments and/or Therapies

- Any prior treatment with interferon

- Any prior treatment with dasatinib

- Any prior treatment with imatinib

- Any other prior systemic treatments, with anti-CML activity [except for
anagrelide, or hydroxyurea (HU)].

- Patients currently taking drugs that are generally accepted to have a risk of causing
Torsades de Pointes as described in Appendix 3.
Study chairs or principal investigatorsSatu Mustjoki, MD, PhD, Principal Investigator, Helsinki University Central Hospital, helsinki, Finland
Henrik Hjorth-Hansen, MD, PhD, Study Chair, St Olavs Hospital, Trondheim, Norway
Ole Weiss-Bjerrum, MD, PhD, Study Chair, Rigshospitalet Copenhagen Denmark
Ingunn Dybedal, MD, PhD, Study Chair, Rikshospitalet, Oslo, Norway
Tobias Gedde-Dahl, MD, PhD, Study Chair, Rikshospitalet, Oslo, Norway
Kimmo Porkka, MD, PhD, Study Chair, Helsinki University Central Hospital, Helsinki, Finland
Johan Richter, MD, PhD, Study Chair, University of Lund, Lund, Sweden
Bengt Simonsson, MD, PhD, Study Chair, University Hospital, Uppsala, Sweden
Leif Stenke, MD, PhD, Study Chair, Karolinska University Hospital, Stockholm, Sweden
LocationsFinland

Helsinki University Central Hospital
Helsinki
00029

Norway

Bergen University Central Hospital
Bergen

Norway

Rikshospitalet
Oslo
0027

Norway

St. Olavs Hospital
Trondheim
7006

Sweden

Lund University Hospital
Lund
22185

Sweden

Karolinska University Hospital
Stockholm
17176

Sweden

Uppsala University Hospital
Uppsala
75185
Study ID numbers2008-004106-13
Last updatedNovember 18, 2011
Record first receivedFebruary 26, 2009
ClinicalTrials.gov identifierNCT00852566
Download dateInformation obtained from ClinicalTrials.gov on February 23, 2012
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