CML Treated With Bosutinib After Relapse
- Registration Number
- NCT02445742
- Lead Sponsor
- PETHEMA Foundation
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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.
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ECOG Performance Status of 0 or 1.
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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:
- Absolute neutrophil count > 1000/mm3 (>1000 x109/L)
- Platelets ≥ 100,000/mm3 (>100 x109/L)
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Bosutinib Bosutinib 500 mg/day of Bosutinib during the study until disease progression, unacceptable toxicity, or withdrawal of consent occurs
- Primary Outcome Measures
Name Time Method Safety measured as adverse event gradation 2 years Safety measured as graded adverse events described on common terminology criteria for adverse events
- Secondary Outcome Measures
Name Time Method Efficacy measured as response rate 2 years Eficaccy measured as response rate to treatment
Trial Locations
- Locations (13)
C. H. U. de Gran Canaria Dr. Negrín
🇪🇸Gran Canaria, Spain
H. U. Son Espases
🇪🇸Palma de Mallorca, Spain
Clínica Quirón Zaragoza S.A.
🇪🇸Zaragoza, Spain
C. Asistencial U. de Salamanca
🇪🇸Salamanca, Spain
C. U. La Paz - H. U. La Paz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
C. H. U. de Santiago
🇪🇸Santiago de Compostela, Spain
C. H. Regional de Málaga , H. General
🇪🇸Málaga, Spain
C. H. Gregorio Marañón
🇪🇸Madrid, Spain
H. Ramón y Cajal
🇪🇸Madrid, Spain
H. U. de la Princesa
🇪🇸Madrid, Spain
H. U. Fundación Jiménez Díaz
🇪🇸Madrid, Spain
H. Virgen de la Salud
🇪🇸Toledo, Spain