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
- Conditions
- Chronic myeloid leukemia (CML) in chronic phase (CP) at diagnosis (untreated)MedDRA version: 9.1Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemia
- Registration Number
- EUCTR2008-004106-13-FI
- Lead Sponsor
- niversity of Trondheim, NTNU, Norway
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 40
1.Patients are able to provide written informed consent
2.Patients must have CML in CP as defined in the protocol
3.Patients must be enrolled in this study within 90 days after the date of first being diagnosed with CML
4.ECOG Performance Status (PS) Score 0 - 1 (see Appendix 2)
5.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.
6.Adequate renal function defined as serum creatinine = 2 times the institutional ULN.
7.Men and women, ages 18 years and older.
8.Adequate BM aspiration sample before the start of study treatment (i.e sample is sufficient for stem cell analysis)
9.Potentially fertile women must use an adequate method of contraception to avoid pregnancy throughout the study.
10.Potentially fertile women must have a negative serum or urine pregnancy test
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Fertile women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study
2.Women who are pregnant or breastfeeding.
3.Men with fertile sexual partners who can or will not use an acceptable contraception method for the entire study
4.A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy.
5.Known pleural effusion at baseline.
6.Uncontrolled or significant cardiovascular disease, including any of the following:
•A myocardial infarction within 6 months
•Uncontrolled angina within 3 months
•Congestive heart failure within 3 months
•Diagnosed or suspected congenital long QT syndrome
•Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe)
•Prolonged QTcF interval > 450 msec on pre-entry ECG
7.History of significant bleeding disorder unrelated to CML, including:
•Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)
•Diagnosed acquired bleeding disorder within one year (e.g., acquired antifactor VIII antibodies).
8.Prior chemotherapy for peripheral stem cell mobilization. (Prior collection of unmobilized peripheral blood stem cells is permitted).
9.Inadequate BM aspiration sample due to marrow fibrosis or other reasons
10.Prior or concurrent malignancy, except for the following:
•adequately treated basal cell or squamous cell skin cancer
•cervical carcinoma in situ
•adequately treated Stage I or II cancer from which the subject is currently in complete remission
•any other cancer from which the subject has been disease-free for three years.
11.Severe psychiatric illness, imprisonment or mental impairment inflicting on ability to give informed consent
12.Abuse of alcohol, prescribed or illicit drugs
13.Evidence of digestive dysfunction that would prevent administration of study therapy by mouth.
14.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)].
15. Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes as described in Appendix 3. Patients who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is greater) prior to the first dose of study therapy. Amiodarone must be discontinued for at least 14 days prior to randomization.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Comparison of proportion of Ph-positive leukemic cells in stem cell compartments (CD34+CD38neg and CD34+CD38+) at 6 months between the study arms (imatinib 400 mg vs. dasatinib 100 mg daily);Secondary Objective: 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 end point(s): The primary endpoint is a comparison of proportion of Ph-positive cells in stem cell compartments (CD34+CD38negand CD34+CD38+) at 6 months between the 2 study arms
- Secondary Outcome Measures
Name Time Method