NL-OMON54687招募中2 期
A Phase I/II study of Bosutinib in pediatric patients with newly diagnosed chronic phase or resistant/intolerant Ph+ Chronic Myeloid Leukemia,ITCC-054/AAML1921 - Bosutinib in pediatric CM
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 10
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 2 至 17（—）
入选标准
- •Phase 1 (R/I patients only)
- •1. Cytogenetic and molecular diagnosis of Philadelphia chromosome positive CML
- •at either time of initial CML diagnosis or at time of study screening:
- •-Cytogenetics must be performed by chromosome banding analysis
- •(CBA) of bone marrow cell metaphases, and requires at least 20 metaphases.
- •-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.
- •-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). 2. Resistance (suboptimal response or failure, as
- •defined by 2013
- •European Leukemia Net guidelines) or intolerance (with or without suboptimal
- •response or failure) to at least one prior tyrosine kinase inhibitor (TKI).
- •The 2013 European LeukemiaNet guidelines will be used to define suboptimal
- •response and failure to prior TKI therapy. Details are provided in appendices 3
- •-Intolerance to prior TKI therapy will be determined by the treating
- •investigator, but generally applies to patients who are unable to receive
- •standard or reduced doses of a TKI due to significant drug-related toxicity
- •and/or when the drug-related toxicity is not responding to appropriate medical
- •management. Patients who enroll as a result of intolerance to prior TKI therapy
- •may have any level of response to their prior therapy and still be eligible.
- •3. Age >=1 and <18 years at day of attaining the informed consent.
- •4. Lansky performance status >=50% for patients <=16 years of age, or Karnofsky
- •scale >=50% for patients >16 years of age (appendix 5).
- •5. Adequate bone marrow function:
- •-For second-line and third-line CP CML patients:
- •-Absolute neutrophil count >1000/mm3 (>1.0 x109/L);
- •-Platelets >=75,000/mm3 (>=75 x109/L) without any platelet transfusions during
- •the preceding 7 days.
- •-For fourth-line CP and all for all AP/BP CML patients:
- •-Absolute neutrophil count >500/mm3 (>0.5 x109/L);
- •-Platelets >=50,000/mm3 (>=50 x109/L) without any platelet transfusions during
- •the preceding 7 days.
- •6. Adequate Renal Function: Subjects must have a calculated creatinine
- •clearance (CrCl) >= 60 mL/min/1.73 m2, using the Schwartz formula to estimate
- •GFR (see appendix 11).
- •7. Adequate liver function, including:
- •AST/ALT <=2.5 x upper limit normal (ULN) or <=5 x ULN if attributable to
- •disease involvement of the liver;
- •Total bilirubin <=1.5 x ULN unless the patient has documented Gilbert syndrome.
- •8. Recovered to Grade 0-1, or to baseline, from any acute toxicities of prior
- •chemotherapy, immunotherapy, radiotherapy, differentiation therapy, or biologic
- •therapy, with the exception of alopecia
- •9.Able to reliably swallow whole capsules, whole tablets, or drug substance
- •(from capsule contents) added to a suitable foodstuff.
- 另有 2 项未显示
排除标准
- •Phase 1 (R/I patients only):
- •1. Diagnosis of primary Ph+ acute lymphoblastic leukemia.
- •2. In patients with AP/BC 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.
- •3. Extramedullary disease only.
- •4. 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).
- •5. Any prior treatment with a TKI within 7 days prior to study entry, or other
- •anti-tumor or anti-leukemia treatment (with the exception of hydroxyurea and/or
- •anagrelide) within 14 days prior to study entry.
- •6. Prior growth factors or biologic agents within 7 days prior to study entry.
- •7. Concomittant use of moderate or strong CYP3A inducers/inhibitors (see
- •appendix 8)within 7 days prior to study entry and during treatment.
- •8. Concomittant use of proton pump inhibitors within 7 days prior to study
- •entry and during treatment.
- •9. Prior radiotherapy within 3 months prior to study entry.
- •10. Allogeneic stem cell transplantation within 3 months prior to study entry.
- •11. Donor lymphocyte infusion (DLI) within 1 month prior to study entry.
- •12. Hereditary bone marrow failure disorder.
- •13. Graft-versus-host disease (GVHD) within 60 days prior to study entry.
- •14. Major surgery within 14 days prior to study entry (recovery from any
- •previous surgery should be complete before day 1).
- •15. History of clinically significant or uncontrolled cardiac disease,
- •History of or active congestive heart failure;
- •Clinically significant ventricular arrhythmia (such as ventricular
- •tachycardia, ventricular fibrillation, or Torsades de pointes);
- •Diagnosed or suspected congenital or acquired prolonged QT syndrome;
- •History of prolonged QTc.
- •16. Prolonged QTc (>450 msec, average of triplicate ECGs).
- •17. Need for medications known to prolong the QT interval.
- •18. Pregnant and/or nursing women
- •19. Uncorrected hypomagnesemia or hypokalemia due to potential effects on the
- •QT interval.
- •20. Left ventricular ejection fraction <50% or shortening fraction <28%.
- •21. Recent or ongoing clinically significant gastrointestinal disorder that may
- •interfere with the intake or absorption of the drug.
- •22. Evidence of serious active or uncontrolled bacterial, fungal or viral
- •23. Known history of hepatitis B (HBV), hepatitis C (HCV), or human
- •immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome
- •(AIDS)-related illness.
- •24. 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,
- 另有 5 项未显示
研究者
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