BOSTRO: CML Treated With Bosutinib After Relapse
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Bosutinib 500 mg/day of Bosutinib during the study until disease progression, unacceptable toxicity, or withdrawal of consent occurs |
Drug: Bosutinib
500 mg/day of Bosutinib during the study until disease progression, unacceptable toxicity, or withdrawal of consent occurs
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- Efficacy measured as response rate [2 years]
Eficaccy measured as response rate to treatment
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed and dated informed consent form.
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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
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Able to take daily oral capsules
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Adequate bone marrow function:
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Absolute neutrophil count > 1000/mm3 (>1000 x109/L)
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Platelets ≥ 100,000/mm3 (>100 x109/L)
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absent any platelet transfusions during the preceding 14 days.
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Adequate hepatic, and renal function:
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AST/ALT ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN if attributable to liver involvement of leukemia
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Total bilirubin ≤ 1.5 × ULN
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Creatinine ≤ 1.5 × ULN
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Age > 18 years
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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
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Subjects with Philadelphia chromosome and bcr-abl negative CML.
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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.
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Subjects with extramedullary disease only.
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Prior stem cell transplantation.
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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)
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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.
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Concomitant use of or need for medications known to prolong the QT interval
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Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval
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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)
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Pregnant or breastfeeding women
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Evidence of serious active infection, or significant medical or psychiatric illness
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | C. H. U. de Gran Canaria Dr. Negrín | Gran Canaria | Spain | ||
| 2 | C. H. Gregorio Marañón | Madrid | Spain | ||
| 3 | C. U. La Paz - H. U. La Paz | Madrid | Spain | ||
| 4 | H. Ramón y Cajal | Madrid | Spain | ||
| 5 | H. U. de la Princesa | Madrid | Spain | ||
| 6 | H. U. Fundación Jiménez Díaz | Madrid | Spain | ||
| 7 | Hospital Universitario 12 de Octubre | Madrid | Spain | ||
| 8 | C. H. Regional de Málaga , H. General | Málaga | Spain | ||
| 9 | H. U. Son Espases | Palma de Mallorca | Spain | ||
| 10 | C. Asistencial U. de Salamanca | Salamanca | Spain | ||
| 11 | C. H. U. de Santiago | Santiago de Compostela | Spain | ||
| 12 | H. Virgen de la Salud | Toledo | Spain | ||
| 13 | Clínica Quirón Zaragoza S.A. | Zaragoza | Spain |
Sponsors and Collaborators
- PETHEMA Foundation
Investigators
- Study Chair: Luis Felipe Casado, Dr, PETHEMA Foundation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BOS-IIG-01