A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- EMD Serono
- 入组人数
- 124
- 试验地点
- 10
- 主要终点
- Dose-Limiting Toxicity (DLT)
研究概览
简要总结
EMD Serono decided to terminate enrollment based on a review of the available clinical data and low probability of completing the trial based on the observed recruitment rate. Subjects already enrolled in the study continued participation in the study, consistent with the protocol, to study completion.
详细描述
The goal of this research study is to investigate for the first time the safety and tolerability of a new drug (AS703569), called an aurora kinase inhibitor, being tested to treat blood cancers in patients with different blood cancers. The research study will also assess how the body breaks down AS703569 and what changes occur in the blood after oral doses of AS703569. It will also look to see if there is any improvement in your blood cancer. The use of AS703569 in this study is experimental.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Dose-escalation part:
- •Primary or secondary acute myeloid leukaemia, including subjects:
- •with first or subsequent relapse after standard therapy, with no established treatment options; refractory to available therapies, e.g. who failed to achieve complete remission after chemotherapies; Newly-diagnosed elderly subjects (over 60 years) according to WHO classification (≥20 blasts in bone marrow), who did not accept or were not eligible for chemotherapy (first line therapy)
- •Subjects with myelodysplastic syndrome (IPSS Int-2 or high risk) resistant or intolerant to standard treatment and not candidates for allogeneic HSCT.
- •Subjects with chronic myeloid leukaemia in chronic, accelerated or blast-phase, resistant or intolerant to standard treatment and not candidates for allogeneic HSCT.
- •Subjects with myeloproliferative disorders and no effective treatment options.
- •Subjects with acute lymphoblastic leukaemia, relapsing, resistant or intolerant to standard treatment and no effective treatment options.
- •Subjects with chronic lymphocytic leukaemia, relapsing, resistant or intolerant to standard treatment and no effective treatment options.
- •Subjects with non-Hodgkin lymphoma, relapsing, resistant or intolerant to standard treatment with no effective treatment options.
- •Cohort expansion part
- •Primary or secondary acute myeloid leukaemia not eligible for chemotherapy (first line therapy), including subjects
- •with first or subsequent relapse after standard therapy, for whom no established treatment options are available; refractory to available therapies, e.g. who failed to achieve complete remission after chemotherapies; Newly-diagnosed elderly subjects (over 60 years) according to WHO classification (≥ 20 blasts in bone marrow), who did not accept or were not eligible for chemotherapy (first line therapy)
- •Subjects with chronic myeloid leukaemia in chronic or accelerated phase, resistant or intolerant to standard treatment, who have not achieved a complete haematological response, and are not candidates for allogeneic HSCT.
- •Subjects with myeloproliferative disorders with no effective treatment options.
- •Subjects with Philadelphia chromosome positive acute leukaemias including acute lymphoblastic leukaemia and blast phase chronic myeloid leukaemia, relapsing, resistant or intolerant to standard treatment with no effective treatment options.
排除标准
- •Acute promyelocytic leukaemia.
- •Ongoing uncontrolled bacterial, viral, fungal or atypical mycobacterial infection.
- •Hyperleukocytosis with >50x10(9)/L leukaemic blasts.
- •Chemotherapy, immunotherapy, biologic therapy or any experimental anti-cancer therapy within 28days prior to study Day1 and/or not having recovered from its toxicity.
- •Extensive radiotherapy involving ≥30% of bone marrow (e.g. whole pelvis, half spine) within 6months prior to study Day
- •Active CNS disease involvement.
- •Any condition, including laboratory, medical history or pre-study assessment findings, that in the opinion of the Investigator, constitute a risk or contraindication for participation or that could interfere with the study objectives, conduct or evaluation of a drug to be taken orally.
- •Clinically relevant cardiac abnormalities or clinically relevant abnormalities .
- •Known infection with human immunodeficiency virus, active hepatitis B, or hepatitis C.
- •Signs and symptoms suggestive of transmissible spongiform encephalopathy.
- •Major surgery within 2weeks prior to study Day
- •Haemoglobin <8g/dL at screening (can be transfused).
- •Refractory to platelet transfusion (defined as increase of <20.109/L platelets 1hour after transfusion).
- •Coexistent second malignancy or history of prior malignancy within previous 3years (excluding basal or squamous cell carcinoma of the skin, and in situ carcinoma of the cervix that has been treated curatively).
研究组 & 干预措施
Regimen 1
Regimen 1: AS703569 administered on Days 1, 2, 3 and Days 8, 9, 10 of a 21-day cycle
干预措施: AS703569 (Drug)
Regimen 2
Regimen 2: AS703569 administered on Days 1, 2, 3, 4, 5, 6 of a 21-day cycle
干预措施: AS703569 (Drug)
结局指标
主要结局
Dose-Limiting Toxicity (DLT)
时间窗: 21 days or 1 cycle
Dose-escalation part - The number of subjects experiencing at least a Dose-Limiting Toxicity (DLT), judged to be related to the study medication, evaluated over the first cycle only for each dose level and regimen, independently.
Preliminary anti-tumour activity
时间窗: 42 days or 2 cycles
Cohort expansion part - Preliminary anti-tumour activity in four selected cohorts of haematological malignancies as assessed every two cycles
次要结局
- Treatment-emergent adverse events (TEAE)(minimum 21 days or 1 cycle)