CML Treated With Bosutinib After Relapse

• Status: Completed
• Trial end date: 2019-06-27
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PETHEMA Foundation

Criteria

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.