Chronic Myeloblastic Leukaemia
Conditions
Keywords
Chronic Myeloblastic Leukaemia
Brief summary
Prospective, open label, multicenter, phase II study evaluating correlation of SNPs with efficacy and toxicity in patients treated with Bosutinib. A total of 50 patients with previously treated Ph+ chronic phase CML will be included in the study
Interventions
DRUGBosutinib
500 mg/day of Bosutinib during the study until disease progression, unacceptable toxicity, or withdrawal of consent occurs
Sponsors
PETHEMA Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent form. * Patients with chronic Ph + CML who presented a non-optimal response at 3 months prior to ITK treatment (imatinib, nilotinib, dasatinib). It is defined as a non-optimal response: BCR-ABL\> 10% per qRT-PCR (IS) at 3 months of initiation of treatment. BCR / ABL ≥ 1% per qRT-PCR (IS) at 6 months of initiation of treatment. BCR / ABL\> 0.1% qRT-PCR (IS) at 12 months of initiation of treatment. BCR-ABL1\> 0.1% qRT-PCR (IS) at any time after 12 months of treatment initiation. * ECOG Performance Status of 0 or 1. * Recovery at Grade 0-1, or at the baseline value of any pretreatment toxicity, except for alopecia. Cases with significant toxicity will be analyzed individually by the study coordinators * Able to take daily oral capsules * Adequate bone marrow function: 1. Absolute neutrophil count \> 1000/mm3 (\>1000 x109/L) 2. Platelets ≥ 100,000/mm3 (\>100 x109/L) 3. absent any platelet transfusions during the preceding 14 days. * Adequate hepatic, and renal function: * AST/ALT ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN if attributable to liver involvement of leukemia * Total bilirubin ≤ 1.5 × ULN * Creatinine ≤ 1.5 × ULN * Age \> 18 years * Willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use reliable methods of birth control (oral contraceptives, intrauterine devices, or barrier methods used with a spermicide) for the duration of the study and for 30 days after the last dose of Bosutinib.
Exclusion criteria
* Subjects with Philadelphia chromosome and bcr-abl negative CML. * Overt leptomeningeal leukemia. Subjects must be free of CNS involvement for a minimum of 2 months. Subjects with symptoms of CNS involvement must have a diagnostic lumbar puncture prior to study enrollment. * Subjects with extramedullary disease only. * Prior stem cell transplantation. * Major surgery within 14 days or radiotherapy within 7 days before the first dose of Bosutinib (recovery from any previous surgery should be complete before day 1) * A history of a clinically significant ventricular arrhythmia, congenital or acquired prolonged QT interval, a baseline QTcF \> 0.47 sec (average of triplicate readings) or unexplained syncope, uncontrolled or symptomatic congestive heart failure (CHF) within 3 months, or myocardial infarction (MI) within 6 months. * Concomitant use of or need for medications known to prolong the QT interval * Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval * Recent (within 30 days of study entry) or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, short bowel syndrome, bleeding, or grade \>1 diarrhea, nausea or emesis lasting more than 2 days, despite adequate medical therapy) * Pregnant or breastfeeding women * Evidence of serious active infection, or significant medical or psychiatric illness * Known seropositivity to HIV, or current acute or chronic Hepatitis B or Hepatitis C (antigen positive), cirrhosis, hypokalemia (any grade), or clinically significant abnormal laboratory finding that would, in the investigator's judgment, make the subject inappropriate for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety measured as adverse event gradation | 2 years | Safety measured as graded adverse events described on common terminology criteria for adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy measured as response rate | 2 years | Eficaccy measured as response rate to treatment |
Countries
Spain
Outcome results
None listed