CML Treated With Bosutinib After Relapse

Phase 2

Completed

• Conditions: Chronic Myeloblastic Leukaemia
• Interventions: Drug: Bosutinib

• 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

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-05-06
• Study First Submitted QC: 2015-05-12
• Study First Posted: 2015-05-15
• Primary Completion: 2018-12
• Study Completion: 2019-06-27
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-28
• Last Update Posted: 2020-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Exclusion Criteria

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