NCT01431664已完成1 期
A Cancer Research UK Phase I/IIa Trial of AT9283 (A Selective Inhibitor of Aurora Kinases) Given Over 72 Hours Every 21 Days Via Intravenous Infusion in Children and Adolescents Aged 6 Months to 18 Years With Relapsed and Refractory Acute Leukemia
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 5
- 主要终点
- Maximum-tolerated dose and recommended phase II dose of multikinase inhibitor AT9283
研究概览
简要总结
RATIONALE: AT9283 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/IIa clinical trial is studying the side effects and best dose of AT9283 in treating young patients with relapsed or refractory acute leukemia.
详细描述
OBJECTIVES:
Primary
- To identify the maximum-tolerated dose and recommended phase IIb dose of multikinase inhibitor AT9283 in pediatric patients with relapsed or refractory acute leukemia.
Secondary
- To evaluate the safety and tolerability of this drug in these patients.
- To document evidence of efficacy of this drug in these patients.
- To investigate the pharmacokinetic profile of this drug in plasma in these patients.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed acute leukemia according to the following criteria:
- •Acute lymphoblastic leukemia (ALL) meeting any of the following criteria:
- •Second relapse
- •Refractory to induction therapy for first relapse
- •Third or subsequent relapse
- •Acute myeloid leukemia (AML) meeting any of the following criteria:
- •Second or subsequent relapse
- •Refractory to an induction therapy for first relapse
- •Without a curative treatment option
- •Other type of acute leukemia meeting any of the following criteria:
- •First or subsequent relapse
- •Refractory to induction therapy
- •Not eligible for any therapy of higher curative potential
- •No chronic myeloid leukemia (CML)
- •Patients in relapse must have ≥ 5% blasts in the bone marrow
- •Patients with refractory disease following induction must have ≥ 20% blasts in the bone marrow
- •No evidence of CNS disease
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status (PS) 50-100% OR Lansky PS 50-100%
- •Life expectancy ≥ 8 weeks
- •Serum bilirubin < 1.5 times upper limit of normal (ULN)
- •ALT or AST < 2.5 times ULN (5 times ULN if due to leukemic infiltration of the liver)
- •Creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile female patients must use 2 of the following combined forms of contraception (oral, injected, or implanted hormonal contraception and condom OR intra-uterine device and condom OR diaphragm with spermicidal gel and condom) before, during, and for 6 months after completion of study therapy
- •Male patients must use 1 form of highly effective contraception (condom plus spermicidal gel) during and for 6 months after completion of study therapy
- •Men with pregnant or lactating partners should be advised to use barrier-method contraception (condom plus spermicidal gel)
- •No serological positivity for hepatitis B, hepatitis C, or HIV
- •No congenital heart disease, with the exception of patent foramen ovale or small muscular ventricular septal deficit (within the first year of life)
- •No uncontrolled arterial hypertension (defined as a systolic blood pressure [BP] and/or diastolic BP ≥ 95th percentile for age and height)
- •No fractional shortening of ≤ 29% on echocardiogram
- •No active graft-vs-host disease
- •No current non-malignant systemic disease considered high medical risk, including any of the following:
- •Active uncontrolled infection
- •Unstable or uncompensated respiratory or cardiac condition that makes study participation undesirable
- •No other condition that, in the Investigator's opinion, would not make the patient a good candidate for the clinical trial
- •PRIOR CONCURRENT THERAPY:
- •Recovered from toxicity of prior therapy, including toxicity following hematopoietic stem cell transplantation
- •Alopecia or certain grade 1 toxicities allowed at the discretion of the Investigator
- •A maximum of 2 days of hydroxycarbamide 10-20 mg/kg/day (or according to local practice) in patients with AML and hyperleukocytosis allowed
- •At least 7 days since prior investigational drugs (except antibodies for which a 4-week window must be observed)
- •At least 7 days since prior protein kinase inhibitors and intrathecal therapy
- •Concurrent intrathecal therapy allowed from course 2 onwards in patients with ALL
- •At least 14 days since prior cytotoxic therapy, including vincristine and other anti-neoplastics
- •No prior major thoracic or abdominal surgery from which the patient has not yet recovered
- •No prior aurora kinase inhibitor
- •No concurrent steroid therapy
- •Multikinase inhibitor AT9283 administration may be commenced once steroids have started; however, steroids may not be started once multikinase inhibitor AT9283 has started
- 另有 4 项未显示
排除标准
- 未提供
结局指标
主要结局
Maximum-tolerated dose and recommended phase II dose of multikinase inhibitor AT9283
次要结局
- Partial remission, complete remission, or complete remission with incomplete bone marrow recovery using disease-specific criteria based on ANC, platelets, and % blasts in the bone marrow
- Plasma concentration measurement of multikinase inhibitor AT9283
- Tertiary outcome(s) - Ex vivo and in vivo measurement of kinase inhibition using Plasma Inhibitory Activity (PIA) assay, phosphorylated STAT5 assay, and skin-punch biopsy (measuring pHH3, p53, PCNA, Ki67 levels)
- Adverse events to multikinase inhibitor AT9283 and grading severity according to NCI CTCAE Version 4.02
- Results of established and novel prognostic biomarkers (genetic mutations of JAK 1, 2, 3, FLT3, IKAROS, and BCR/ABL) linking to observed responses
研究者
研究点 (5)
Loading locations...
相似试验
已完成
1 期
AT9283 in Children and Adolescents With Relapsed and Refractory Solid TumorsUnspecified Childhood Solid Tumor, Protocol SpecificNCT00985868Cancer Research UK33
已完成
1 期
Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's LymphomaNon-Hodgkins LymphomaUnspecified Adult Solid Tumor, Protocol SpecificNCT00443976NCIC Clinical Trials Group35
进行中（未招募）
1 期
AT9283 in children and adolescents with acute leukaemiaRelapsed and refractory acute leukaemiaMedDRA version: 14.1 Level: PT Classification code 10000830 Term: Acute leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2009-016952-36-GBCancer Research UK7
已完成
1 期
AT9283 in children and adolescents with acute leukaemiaAcute LeukaemiaAcute lymphoblastic & acute myeloid leukaemiaCancerISRCTN97388141Cancer Research UK7
已完成
1 期
MK0752 and Gemcitabine Hydrochloride in Treating Patients With Stage III and IV Pancreatic Cancer That Cannot Be Removed by SurgeryPancreatic CancerNCT01098344Cancer Research UK44