Clinical trial NCT02445742: CML Treated With Bosutinib After Relapse
Official title: Single Nucleotide Polymorphism Association With Response and Toxic Effects in Patients With Ph+ CP-CML Treated With Bosutinib After Relapse to Previous Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloblastic Leukaemia
Keywords: Chronic Myeloblastic Leukaemia
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2015-05-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Safety measured as adverse event gradation
timeFrame: 2 years
Secondary outcomes:
measure: Efficacy measured as response rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Gran Canaria
country: Spain
facility: C. H. U. de Gran Canaria Dr. Negrín
city: Madrid
country: Spain
facility: C. H. Gregorio Marañón
city: Madrid
country: Spain
facility: C. U. La Paz - H. U. La Paz
city: Madrid
country: Spain
facility: H. Ramón y Cajal
city: Madrid
country: Spain
facility: H. U. de la Princesa
city: Madrid
country: Spain
facility: H. U. Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: C. H. Regional de Málaga , H. General
city: Palma de Mallorca
country: Spain
facility: H. U. Son Espases
city: Salamanca
country: Spain
facility: C. Asistencial U. de Salamanca
city: Santiago de Compostela
country: Spain
facility: C. H. U. de Santiago
city: Toledo
country: Spain
facility: H. Virgen de la Salud
city: Zaragoza
country: Spain
facility: Clínica Quirón Zaragoza S.A.
Study officials:
affiliation: PETHEMA Foundation
name: Luis Felipe Casado, Dr
role: STUDY_CHAIR
References: