CML Treated With Bosutinib After Relapse (BOSTRO)

Single Nucleotide Polymorphism Association With Response and Toxic Effects in Patients With Ph+ CP-CML Treated With Bosutinib After Relapse to Previous Treatment

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

Study Overview

• Status: Completed
• Conditions: Chronic Myeloblastic Leukaemia
• Intervention / Treatment: Drug: Bosutinib

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Gran Canaria, Spain
    • C. H. U. de Gran Canaria Dr. Negrín
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • H. Ramón y Cajal
  • Madrid, Spain
    • C. H. Gregorio Marañón
  • Madrid, Spain
    • C. U. La Paz - H. U. La Paz
  • Madrid, Spain
    • H. U. de la Princesa
  • Madrid, Spain
    • H. U. Fundación Jiménez Díaz
  • Málaga, Spain
    • C. H. Regional de Málaga , H. General
  • Palma de Mallorca, Spain
    • H. U. Son Espases
  • Salamanca, Spain
    • C. Asistencial U. de Salamanca
  • Santiago de Compostela, Spain
    • C. H. U. de Santiago
  • Toledo, Spain
    • H. Vírgen de la Salud
  • Zaragoza, Spain
    • Clínica Quirón Zaragoza S.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Bostro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety measured as adverse event gradation	Safety measured as graded adverse events described on common terminology criteria for adverse events	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy measured as response rate	Eficaccy measured as response rate to treatment	2 years

Collaborators and Investigators

• Sponsor: PETHEMA Foundation
• Investigators: Study Chair: Luis Felipe Casado, Dr, PETHEMA Foundation

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): June 27, 2019

Study Registration Dates

• First Submitted: May 6, 2015
• First Submitted That Met QC Criteria: May 12, 2015
• First Posted (Estimate): May 15, 2015

Study Record Updates

• Last Update Posted (Actual): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Chronic Myeloblastic Leukaemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Leukemia, Myeloid; Recurrence
• Other Study ID Numbers: BOS-IIG-01