An Open-Label, Randomized, Multicenter Phase III Trial of Dasatinib (SPRYCEL ) vs. Standard Dose Imatinib (400 mg) in the Treatment of Subjects with Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia.
- Conditions
- -C921 Chronic myeloid leukaemia [CML], BCR/ABL-positiveChronic myeloid leukaemia [CML], BCR/ABL-positiveC921
- Registration Number
- PER-071-07
- Lead Sponsor
- BRISTOL MYERS SQUIBB COMPANY,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 18
• Patients will have to provide informed consent in writing;
• Patients should have CML in Ph + CF, defined by the presence of all the criteria indicated below: 15% of blasts in peripheral blood and in bone marrow. <30% blisters plus promyelocytes in peripheral blood and bone marrow. <20% of basophils in peripheral blood. > 100 X 10 9 platelets / liter.
• Chronic CML not previously treated [less than 4 weeks (28 days) of imatinib allowed as long as the patient has not experienced hematogenic or non-haematological toxicity of Grade 3-4 attributed to imatinib].
• Patients must enroll in this study within approximately 3 months (90 days) after the date they were first diagnosed with CML, based on the results of the bone marrow cytogenetics test that they demonstrated the presence of the Philadelphia chromosome or of the translocation variants (9; 22). Patients may still be eligible if they have secondary chromosomal abnormalities (ie, clonic evolution) in addition to the Philadelphia chromosome.
• 0 - 2 score on the Performance Status (PS) scale of the ECOG (see
• Adequate liver function defined as; total bilirubin <2.0 times the institutional ULN: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 times the upper limit of the institutional normal (LSN).
• Adequate renal function defined as serum creatinine <3 times the institutional ULN.
• Men and women 18 years of age or older.
• Women of childbearing age (FEM) should use a method of birth control that is adequate to avoid pregnancy throughout the study and for a period of at least 1 month (4 weeks) before and at least 1 month (4 weeks) weeks) after the last dose of the investigational product, in such a way as to minimize the risk of becoming pregnant.
• Women of childbearing age should present a negative result in the pregnancy test carried out in serum or urine (minimum sensitivity 25 IU / I, or equivalent units of HCG), 72 hours before the start of the study medication.
• MEF who are not willing or able to use a method of birth control that is acceptable throughout the study and at least 1 month (4 weeks) before and at least 1 month (4 weeks) after the last dose of the study medication;
• MEF who are using a prohibited method of contraception (does not apply to this study);
• Women who are pregnant or breast-feeding;
• Women who have obtained a positive result in the pregnancy test performed during the enrollment, or before the administration of the study drug;
• Men whose sexual partners are MEF, who are not willing or able to use a method that is acceptable to avoid pregnancy of their partner, throughout the study and at least 1 month (4 weeks) after the end of the administration of study medication.
• Severe, uncontrolled medical condition or active infection that could impair the possibility of the subject receiving the protocol therapy;
• Pleural effusion known at the baseline visit;
• Significant or uncontrolled cardiovascular disease, including: myocardial infarction in the previous 6 months, uncontrolled angina in the previous 3 months. Congestive heart failure in the previous 3 months, congenital prolonged QT syndrome, diagnosed or suspected, Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsade des Pointes). prolonged QTc interval> 450 msec in the electrocardiogram prior to admission.
• History of significant bleeding disorder not associated with CML, including: Congenital bleeding disorder diagnosed (eg, von Willebrand disease) Acquired bleeding disorder diagnosed in the course of the previous year (eg, antibodies acquired from anti-factor VIII ) 10) Previous chemotherapy by mobilization of peripheral stem cells (previous immobilized peripheral blood stem cells are allowed).
• Previous or concurrent neoplasia, except for the following: Basal cell or squamous cell skin cancer adequately treated cervical carcinoma in situ adequately treated stage I or II cancer, of which the patient is currently in total remission or any other cancer of which The patient has been free of disease for three years.
• Evidence of digestive dysfunction that would prevent the administration of therapy in the oral study.
• Any previous treatment with interferon
• Any previous treatment with dasatinib
• Any other previous systemic treatment, with activity against CML [with the exception of anagrelide, hydroxyurea (HU) or 4 weeks (28 days) of imatinib].
• Patients currently taking drugs of which it is generally accepted that they can cause Torsades de Pointes as described in section 5.5.1.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:The cytogenetic response (RCy) is based on the prevalence of Ph + cells in metaphase on a sample of bone marrow. Partial Cytogenetic Response fRCvP): from 1 to 35% of Ph + cells in metaphase in the bone marrow.<br>Measure:Rate of the best RCyC confirmed within 12 months.<br>Timepoints:12 months<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:A Complete Blood Response (RHC) is obtained when all criteria are met when performing a peripheral blood test (SP)<br>Measure:Rate of RHC, RCyM and RMM within 12 months<br>Timepoints:12 monjths<br>;<br>Outcome name:The cytogenetic response (RCy) is based on the prevalence of Ph + cells in metaphase on a sample of bone marrow. Partial Cytogenetic Response fRCvP): from 1 to 35% of Ph + cells in metaphase in the bone marrow. A Complete Blood Response (RHC) is obtained when all criteria are met when performing a peripheral blood test (SP)<br>Measure:Best global response at any time for RCyC, RCyM, RHC and RMM<br>Timepoints:12 months<br>;<br>Outcome name:The molecular response will be determined using the measurement of BCR-ABL transcript levels by the polymerase real-time quantitative chain reaction (RQPCR).<br>Measure:Exploration of the spectrum of BCRABL mutations and the level of expression of the BCR-ABL gene.<br>Timepoints:12 months<br>