EUCTR2016-002919-18-SE进行中（未招募）1 期
A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination with Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) with FLT3-ITD mutations.
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 65
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Diagnosis of AML according to the WHO 2008 classification with =5% blasts in bone marrow, with or without extramedullary disease
- •2. Subjects must be in first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1-2 cycles of induction chemotherapy) at remission induction. Prior HSCT is permitted
- •3. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood. Subjects may be enrolled and begin treatment based upon the results of a local FLT3-ITD laboratory test, however, a sample must be sent to the central laboratory for confirmation. Subjects with a negative central FLT3-ITD test who are enrolled and have begun treatment based upon results of a local FLT3-ITD lab test may continue on the study at the investigator's discretion after
- •discussion with the medical monitor.
- •4. Subjects must be between 1 month and =21 years of age at the time the ICF is signed.
- •5. Karnofsky performance status score of >50% for subjects >16 years of age, and a Lansky performance status score of >50% for subjects =16 years of age.
- •6. Subjects must have fully recovered from the acute toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to Re- Induction Cycle 1, Day 1:
- •a. Myelosuppressive chemotherapy:
- •- For subjects who relapse while they are receiving cytotoxic therapy, at least 21 days must have elapsed since the completion of cytotoxic therapy.
- •- Cytoreduction with hydroxyurea can be initiated and continued for up to 1 day prior to the start of systemic protocol therapy. Subjects may also receive low dose cytarabine for cytoreduction and completed up to 1 day prior to the start of systemic protocol therapy.
- •- Subjects who have received other FLT3 inhibitors (e.g., lestaurtinib, sorafenib), with the exception of quizartinib, are eligible for this study.
- •b. Hematopoietic growth factors: At least 3 days since the completion of therapy with a growth factor.
- •c. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. However, for agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the medical monitor.
- •d. =14 days for local external radiation therapy (XRT) for CNS chloromas.
- •e. =90 days must have elapsed if prior total body radiation (TBI) or craniospinal XRT occurred.
- •f. At least 90 days must have elapsed since HSCT. For subjects with a history of (GVHD) Immunosuppressive therapy must be stable for =2 weeks in subjects with a history of = Grade 2 GVHD and for =4 weeks in subjects with a history of Grade 3/4 GVHD.
- •g. Investigational drug/device: at least 30 days or 5 half-lives since the completion of therapy, whichever is longer.
- •7. Adequate renal and hepatic functions as indicated by the following laboratory values:
- •a. Serum creatinine concentration =1.5 × institutional (ULN) based on the age and sex, or (CrCl) >0.84 mL/s. (as measured preferably by a nuclear glomerular filtration rate scan, timed urine collection for CrCl, or
- •calculated by the Schwartz formula [for subjects <18 years] or Cockcroft-Gault [for subjects =18 years] and normalized to a BSA of 1.73m2).
- •b. Total bilirubin <1.5 × ULN for age or normal conjugated bilirubin.
- •c. (ALT) <5 × ULN.
- •8. Left Ventricular (LV) fractional shortening of =29% by echocardiogram, OR a left ventricular ejection fract
排除标准
- •Subjects who meet any of the following criteria will be disqualified from entering the study:
- •1. Diagnosis of isolated CNS relapse (CNS2/3 disease is allowed if treated with additional IT chemotherapy).
- •2. Diagnosis of acute promyelocytic leukemia (APL), juvenile myelomonocytic leukemia (JMML), French-American-British (FAB) classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or myeloid proliferations related to Down syndrome.
- •3. Uncontrolled or significant cardiovascular disease, including:
- •a. Diagnosed or suspected congenital long QT syndrome.
- •b. History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes [TdP]); any history of arrhythmia will be discussed with the medical monitor
- •prior to subject's entry into the study.
- •c. QT interval corrected >450 ms:
- •QTc interval corrected with Bazett's formula (QTcB) for subjects < 6
- •years of age at the time of enrollment.
- •QTc interval corrected with Fridericia’s formula (QTcF) for subjects = 6 years of age at the time of enrollment.
- •d. History of uncontrolled angina pectoris or myocardial infarction within 6 months.
- •e. History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker).
- •f. Heart rate <50 beats/minute on screening electrocardiogram (ECG).
- •g. Uncontrolled hypertension (i.e., systolic blood pressure and /or diastolic blood pressure that is, on repeated measurement, at or above the 95th percentile for sex, age, and height).
- •h. History of complete left bundle branch block.
- •i. History of New York Heart Association Class 3 or 4 heart failure.
- •4. Subjects will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The subject needs to be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systemic protocol therapy.
- •5. Known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C).
- •6. Known history of human immunodeficiency virus (HIV).
- •7. History of hypersensitivity to any of the study medications or their excipients.
- •8. Subject is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol.
- •9. Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results.
- •10. Currently participating in other investigational interventional procedures (does not include observational procedures or long-term follow-up for previous interventional studies).
- •11. Otherwise considered inappropriate for the study by the Investigator.
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