2024-512469-15-00已完成2 期
A Phase 1/2, Multicenter, Open-Label, Single Arm, Dose Escalation and Expansion Study of Gilteritinib (ASP2215) Combined with Chemotherapy in Children, Adolescents and Young Adults with FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 15
- 主要终点
- • Phase 1: Determination of MTD and/or RP2D • Phase 2: o CRc rates (overall best response) after 2 cycles of therapy. o CR rates after 2 cycles of therapy; CR rate will be further described by the duration of CR (only for USA).
研究概览
简要总结
● Phase 1 (Dose Escalation Phase): To determine the maximum tolerated dose (MTD) and/or optimally safe and biologically active recommended phase 2 dose (RP2D) of gilteritinib given in sequential combination with FLAG in children, adolescents and young adults with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3) (internal tandem duplication (ITD) and/or tyrosine kinase domain (TKD) acute myeloid leukemia (AML). ● Phase 2 (Dose Expansion Phase): To determine complete remission (CR) rates and composite complete remission (CRc) rates after 2 cycles of gilteritinib in sequential combination with FLAG in children, adolescents and young adults with FLT3 (ITD) AML who are refractory to or at the first hematologic relapse after first-line remission induction AML therapy (up to 2 induction cycles).
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Phase 1: Subject is positive for FLT3 (ITD and/or TKD) mutation in bone marrow or blood as determined by the local institution. Phase 2: Subject is positive for the FLT3 (ITD) mutation in bone marrow or blood as determined by the local institution.
- •Subject is aged ≥ 6 months and < 21 years of age* at the time of signing informed consent and/or assent, as applicable. * For phase 2: Enrollment of subjects from 6 months to less than 1 year (Group 3) and 1 year to less than 2 years (Group 2) will be dependent on the establishment of RP2D in the respective for age groups during phase
- •Subject has a diagnosis of AML according to The French–American–British (FAB) classification with ≥ 5% blasts in the bone marrow, with or without extramedullary disease (except subjects with active central nervous system (CNS) Leukemia). a) In the phase 1 portion of the study, subject must be in first or greater relapse or refractory to induction therapy with no more than 1 attempt at remission induction (up to 2 induction cycles). b) For the phase 2 portion of the study, subject must be refractory to or at the first hematologic relapse after first-line remission induction AML therapy (up to 2 induction cycles)
排除标准
- •Subject has active central nervous system (CNS) leukemia.
- •Subject has uncontrolled or significant cardiovascular disease, including: • Diagnosed or suspected congenital long QT syndrome or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); any history of arrhythmia will be discussed with the sponsor’s medical monitor prior to subject’s entry into the study • Prolonged Fridericia-corrected QT interval (QTcF) interval on pre-entry electrocardiogram (ECG) (≥ 450 ms) • Any history of second- or third-degree heart block (may be eligible if the subject currently has a pacemaker) • Heart rate < 50 beats/minute on pre-entry ECG • Uncontrolled hypertension • Complete left bundle branch block
- •Subject has active clinically significant graft-versus-host disease (GVHD) or is on treatment with immunosuppressive drugs for treatment of active GVHD, with the exception of subjects being weaned from systemic corticosteroids where the subject is receiving ≤ 0.5 mg/kg of prednisone (or equivalent) daily dose for prior GVHD. Subject has received calcineurin inhibitors within 4 weeks prior to screening, unless used as GVHD prophylaxis
- •Subject has active malignant tumors other than AML.
- •Subject has hypokalemia and/or hypomagnesemia at Screening (defined as values below institutional lower limit of normal [LLN]). Repletion of potassium and magnesium levels during the screening period is allowed.
- •Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A/P-glycoprotein (P-gp).
结局指标
主要结局
• Phase 1: Determination of MTD and/or RP2D • Phase 2: o CRc rates (overall best response) after 2 cycles of therapy. o CR rates after 2 cycles of therapy; CR rate will be further described by the duration of CR (only for USA).
• Phase 1: Determination of MTD and/or RP2D • Phase 2: o CRc rates (overall best response) after 2 cycles of therapy. o CR rates after 2 cycles of therapy; CR rate will be further described by the duration of CR (only for USA).
次要结局
- Acceptability and palatability assessment of the formulation
- EFS rate
- OS rate
- MRD assessment
- Inhibition of phosphorylated FLT3 (pFLT3) measured by PIA assay
- Gilteritinib plasma concentration
- Pharmacokinetic parameters (e.g., oral clearance [CL/F], apparent volume of distribution [Vd/F], maximum concentration [Cmax], time of maximum concentration [tmax], area under the concentration-time curve [AUC]) of gilteritinib
- Safety, tolerability and toxicity assessments of gilteritinib when given in combination with FLAG
研究者
Clinical Trial Unit Head
Scientific
Astellas Pharma Global Development Inc.
研究点 (15)
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