Bosutinib in pediatric CML patients
- Conditions
- Chronic Myeloid LeukemiaMedDRA version: 21.1Level: LLTClassification code: 10009015Term: Chronic myeloid leukemia Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 60
Phase 1 and Phase 2 (R/I patients): Cytogenetic and molecular diagnosis of Philadelphia chromosome-positive CML at either time of initial CML diagnosis or at time of study screening: 1. Cytogenetics must be performed by chromosome banding analysis (CBA) of bone marrow cell metaphases, and requires at least 20 metaphases. 2. Only if dividing marrow cells cannot be obtained, or if there is an insufficient number of metaphases, CBA can be substituted by interphase fluorescence in situ hybridization (I- FISH) of bone marrow or peripheral blood cells, using dual color dual fusion probes, that allow the detection of BCR-ABL+ nuclei; at least 200 nuclei should be counted. 3. Qualitative RT-PCR should be performed on RNA extracted from freshly collected bone marrow or peripheral blood cells. It identifies the transcript type, either e14a2 or 13a2 (also known as b3a2 and b2a2), or much more rarely e19a2, or e1a2, indicating the BCR- ABL protein weight (P210, rarely P230 or P190)., Phase 1 and Phase 2 (R/I patients): Serum/urine pregnancy test (for all girls = age of menarche) negative at screening., Phase 1 and Phase 2 (R/I patients): Male and female patients of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active., Phase 1 and Phase 2 (R/I patients): Written informed consent of parent(s)/legal guardian(s) and/or patients (when applicable depending on age and local law and regulations)., Phase 1 and Phase 2 (R/I patients): Patients (including legally acceptable representative for minors where applicable) who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures., Phase 2 (Newly Diagnosed CML patients): Cytogenetic and molecular diagnosis of Philadelphia chromosome-positive CML at either time of initial CML diagnosis or at time of study screening: 1. Cytogenetics must be performed by chromosome banding analysis (CBA) of bone marrow cell metaphases, and requires at least 20 metaphases. 2. Only if dividing marrow cells cannot be obtained, or if there is an insufficient number of metaphases, CBA can be substituted by interphase fluorescence in situ hybridization (I- FISH) of bone marrow or peripheral blood cells, using dual color dual fusion probes, that allow the detection of BCR-ABL+ nuclei; at least 200 nuclei should be counted. 3. Qualitative RT-PCR should be performed on RNA extracted from freshly collected bone marrow or peripheral blood cells. It identifies the transcript type, either e14a2 or e13a2 (also known as b3a2 and b2a2), or much more rarely e19a2, or e1a2, indicating the BCR- ABL protein weight (P210, rarely P230 or P190)., Phase 2 (Newly Diagnosed CML patients): Newly diagnosed CP Ph+ CML of = 6 months (from initial diagnosis) without any previous TKI treatment (with the exception of hydroxyurea and/or anagrelide) for CML., Phase 2 (Newly Diagnosed CML patients): Age =1 and <18 years at day of attaining the informed consent., Phase 2 (Newly Diagnosed CML patients): Lansky performance status =50% for patients =16 years of age, or Karnofsky scale =50% for patients >16 years of age., Phase 2 (Newly Diagnosed CML patients): Adequate Renal Function: Subject
Phase 1 and Phase 2 (R/I patients): Diagnosis of primary Ph+ acute lymphoblastic leukemia., Phase 1 and Phase 2 (R/I patients): Allogeneic stem cell transplantation within 3 months prior to bosutinib treatment., Phase 1 and Phase 2 (R/I patients): Donor lymphocyte infusion (DLI) within 1 month prior to bosutinib treatment., Phase 1 and Phase 2 (R/I patients): Hereditary bone marrow failure disorder., Phase 1 and Phase 2 (R/I patients): Graft-versus-host disease (GVHD) within 60 days prior to bosutinib treatment., Phase 1 and Phase 2 (R/I patients): Major surgery within 14 days prior to bosutinib treatment (recovery from any previous surgery should be complete before day 1)., Phase 1 and Phase 2 (R/I patients): History of clinically significant or uncontrolled cardiac disease, including: 1. History of or active congestive heart failure; 2. Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); 3. Diagnosed or suspected congenital or acquired prolonged QT syndrome; 4 History of prolonged QTc, Phase 1 and Phase 2 (R/I patients): Prolonged QTc (>450 msec, average of triplicate ECGs)., Phase 1 and Phase 2 (R/I patients): Need for medications known to prolong the QT interval., Phase 1 and Phase 2 (R/I patients): Pregnant and/or nursing women., Phase 1 and Phase 2 (R/I patients): Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval., Phase 1 and Phase 2 (R/I patients): In patients with AP/BP CML: leptomeningeal leukemia, defined as positive cytology on lumbar puncture (including both CNS2 and CNS3 status), or clinical symptoms or signs present. This assessment is not required for inclusion of CP CML patients., Phase 1 and Phase 2 (R/I patients): Left ventricular ejection fraction <50% or shortening fraction <28%., Phase 1 and Phase 2 (R/I patients): Recent or ongoing clinically significant gastrointestinal disorder that may interfere with the intake or absorption of the drug., Phase 1 and Phase 2 (R/I patients): Evidence of serious active or uncontrolled bacterial, fungal or viral infection., Phase 1 and Phase 2 (R/I patients): Known history of hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness., Phase 1 and Phase 2 (R/I patients): Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study., Phase 2 (Newly Diagnosed CML patients): Diagnosis of primary Ph+ acute lymphoblastic leukemia., Phase 2 (Newly Diagnosed CML patients): Extramedullary disease only., Phase 2 (Newly Diagnosed CML patients): Documented prior history of T315I or V299L BCR-ABL1 mutations (Note: BCR-ABL1 mutation testing will be performed at screening for a baseline assessment, but results are not used to determine eligibility. This exclusion criterion is based on whether there is a known history of these mutations at the time of study entry. If these mutations become evident during the study the patient will go off study)., Phase 2 (Newly Diagnosed CML patients): Any prior treatment with a TKI or other anti-tumor or anti-leukemia treatment (with the exception of hydroxyure
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method