None listed
Conditions
Interventions
Arm of BMS-354825 Type of group
Treatment of BMS-354825 will begin with 70 mg PO, IDB, with continuous daily doses administered. Patients in arm BMS-354825 will be increased the dose to 90 mg BID if (1) there is a progression or (2) if there is no RCyM at 12 weeks. If the patient does not tolerate BMS-354825 in any of the administered doses, they will be allowed up to 2 dose reductions
Arm Imatinib Type of group
The doses of imatinib will be 400 mg PO, IDB, and daily doses will be administered continuously. The patients will continue the treatment until an intolerable progression or toxicity is confirmed, and at that moment they can go to the treatment arm BMS-354825, after one week of rest of imatinib. If at 12 weeks the patient does not reach RCyM or an absolute reduction of> 30% in the Ph + metaphases, then a transfer is made to the BMS-54825 arm of the study after one week of rest of imatinib. No in
On the other hand, a dose reduction of 600 mg per day is allowed if the patient has not previously received treatment at that dose level.
Sponsors
BRISTOL MYERS SQUIBB COMPANY,
Eligibility
Inclusion criteria
Inclusion criteria: 1) Informed consent in writen and signed. 2) Available for periodic monitoring. 3) Life expectancy of at least 3 months, approximately. 4) Score 0 - 1 in the performance status ECOG. 5) Patients with Ph + CML in chronic phase. 6) Patients must meet at least one of the following criteria: A) Has been previously treated with imatinib at a dose greater than 600 mg / day and developed progressive disease upon receiving such dose of imatinib. B) CML with resistance to imatinib <600 mg / d with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib. C) Intolerance at any dose of imatinib. 7) Adequate liver function. 8) Adequate renal function. 9) Serum potassium and magnesium levels within the normal institutional limits. 10) Men and women 18 years of age or older
Exclusion criteria
Exclusion criteria: 1) MEF that are not willing or able to use a method of birth control that is acceptable. 2) MEF who are using a prohibited contraceptive method. 3) Women who are pregnant or breastfeeding. 4) Women who have obtained a positive result in the pregnancy test within 72 hours before the administration of the study drug. 5) Sexually active men whose sexual partners are MEF who may become pregnant, who are unwilling or unable to use a method of birth control that is acceptable. 6) Previous diagnosis of CML in accelerated phase or in blast crisis. 7) Patients who are eligible and willing to undergo a transplant during the selection period. 8) Severe uncontrolled medical condition or active infection that could impair the possibility of the patient receiving the protocol therapy. 9) Significant or uncontrolled cardiovascular disease. 10) Dementia or altered mental state that would prevent understanding or granting informed consent. 11) History of significant hemorrhagic disorder not associated with CML. 12) Concurrent incurable malignancy in addition to CML. 13) Evidence of organic dysfunction or digestive dysfunction that would prevent the administration of study therapy. 14) Patients who received any of the following: a) Imatinib within 7 days. b) Interferon or cytarabine within 14 days. c) A small molecule anti-cancer agent target within the previous 14 days. d) Any other antineoplastic or investigational drug, except hydroxyurea or anagrelide, within 28 days prior to the start of treatment with BMS-354825. 15) Individuals who are currently taking drugs are generally accepted that there is a risk that they cause Torsade des Pointes. 16) Individuals who are taking drugs that irreversibly inhibit platelet function. 17) Individuals taking drugs recognized as potent inhibitors or inducers of CYP3A4. 18) Previous therapy with BMS-354825.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Bone marrow biopsy and percentage count of cells with positive Philadelphia chromosome. Measure:High cytogenetic response rate RCyM for BMS-354825. Timepoints:Pre-treatment, at 12 weeks and if there is a transfer to the other arm, it will be done outside the study within 30 days after the last dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Duration of RCyM. Time to RCyM: Bone marrow biopsy and percentage count of cells with positive Philadelphia chromosome. Complete haematological response rate (RHC). Time to RHG. Duration of RHC: 1) White blood cell count 1000 / mm3. 3) Platelets> 100,000 and <upper normal institutional limit. 4) Neither blasts nor promyelocytes in peripheral blood. 5) Blasts in bone marrow <5%. 6) <5% myelocytes plus metamyelocytes in peripheral blood. 7) <20% of basophils in peripheral blood. 8) Without extramedullary commitment. Higher molecular response rate: Bone marrow biopsy and percentage count of cells with positive Philadelphia chromosome. Measure:Duration of RCyM. Time to RCyM. Complete haematological response rate (RHC). Duration of RHC. Time to RHG. High molecular response rate. Timepoints:Bone marrow biopsy and percentage count of cells with positive Philadelphia chromosome: At week 12 and if there is a transfer to the other arm, it will be done before it. Peripheral blood tests: Days 8, 15, 22, 29 and then weekly until week 12 ; Outcome name:Bone marrow biopsy and BCR / ABL PCR Measure:Mutation analysis of BCR / ABL Timepoints:It will be done during visits outside the study. Carried out within 30 days after the last dose of therapy. Or if a transfer occurs, before this. ; Outcome name:FACT-G questionnaire Measure:Quality in health Timepoints:Day 28 and thereafter every 4 weeks during the first 24 weeks and every 12 weeks onwards ; Outcome name:Clinical evaluation Measure:Security of BMS-354825. Timepoints:Days 8, 15, 22, 29 | — |
Countries
Austria, Belgium, Denmark, Estonia, Finland, Germany, Hungary, Ireland, Peru, Spain, Sweden, United Kindgdom
Outcome results
None listed