Phase I/II Study Using Imatinib and s.c. BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia (CML) Patients in First Chronic Phase Achieving Less Than Optimal Response With Imatinib.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients
研究概览
简要总结
The aim of the study is to test the safety and efficacy of BL-8040 (a CXCR4 antagonist) in improving the response to imatinib in CML patients not achieving an optimal response with imatinib alone.
详细描述
To improve cytogenetic and molecular response of CML patients receiving Imatinib, who have not achieved an optimal response according to European LeukemiaNet (ELN) definitions , or MR4 after 24 months with Imatinib. This will be achieved by addition of the CXCR4 antagonist BL-8040, mobilizing CML leukemia stem cells from their protective bone marrow niche and exposing them to Imatinib and BL-8040-mediated apoptosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult men and women subjects aged 18 to 70, inclusive.
- •Confirmed diagnosis of chronic phase CML according to the WHO criteria (WHO 2008)
- •CML patients with sub-optimal response to Tyrosine Kinase Inhibitors, defined as "warning" in the ELN recommendations:
- •Following 3 months: BCR-ABL1 > 10%, and/or Ph+ 36-95% Following 6 months: BCR-ABL1 1-10%, and/or Ph + 1-35% Following 12 months: BCR-ABL1 0.1-1 % Following 24 months: Less than MR4
- •Clinical laboratory values should be as follows:
- •White blood cell count < 30 X 10*9/L Creatinine < 1.5 ULN
- •Women of childbearing potential and all men must agree to use approved form of contraception
- •Subject is able and willing to comply with the requirements of the protocol.
- •Subject is able to voluntarily provide written informed consent.
排除标准
- •CML patients not in chronic phase.
- •CML patients receiving Tyrosine Kinase Inhibitors other than Imatinib.
- •CML patients receiving Imatinib > 400 mg/day.
- •Patients not able to sign informed consent.
- •Known allergy or hypersensitivity to any of the test compounds or materials or contraindication to test product.
- •Low Performance Status (ECOG > 2).
- •Abnormal liver function tests:
- •Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) 2 x upper limit of normal (ULN).
- •Serum bilirubin. Total bilirubin > 2.0 mg/dL (34 µmol/L), conjugated bilirubin > 0.8 mg/dL
- •Abnormal left ventricular ejection fraction, < 40 %.
- •Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to:
- •Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy
- •A co-morbid condition which, in the view of the Investigators, renders the subject at high risk from treatment complications.
- •Women subjects who are pregnant or breastfeeding.
研究组 & 干预措施
BL-8040
Patients with chronic phase CML on Imatinib therapy (400 mg/day) achieving less than an optimal response will be treated with sc injections of BL-8040, while continuing Imatinib. The first part of the study will include escalating dose groups. Up to 4 dose levels will be investigated starting at dose level 1. Patients will be accrued in a conventional 3+3 design. Applying this study design, the first cohort of 3 patients will be treated at dose level 1 (0.5 mg/kg) on Day 1, 15, 29 and 43. Patients will continue taking Imatinib 400 mg/day throughout the study. Dose escalation will continue until the maximal tolerated dose (MTD) is established and protocol specific stopping rules for toxicity are met. If no MTD is reached, dose escalation will continue up to dose level 4 (1.25 mg/kg).
干预措施: BL-8040 (Drug)
结局指标
主要结局
To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients
时间窗: 4 months
The investigators will assess the safety of the BL-8040 by grading of toxicities according to standard Common Toxicity Criteria for Adverse Effects (CTCAE) criteria.
次要结局
- To assess the clinical efficacy of BL-8040 in combination with Imatinib(2 years)