Novel and optimized de-intensified induction therapy in acute myeloid leukemia.
试验速览
- 阶段
- 1/2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 183
- 试验地点
- 3
- 主要终点
- Best response rate (CR+iCR+MLFS) at end of 4 cycles of treatment
研究概览
简要总结
Introduction: Acute myeloid leukemia (AML) is a potentially curable hematological malignancy but remains one of the most challenging and expensive hematological malignancy to manage. In India these challenges are further exacerbated by high incidence of multi-drug resistant infections and a high out of pocket expense that results in a high induction mortality and limited access to therapy for most patients with a diagnosis of AML, using a conventional intensive chemotherapy that is offered for this disease in young adults (<60 years).
There is a felt need to introduce and optimize de-intensified induction therapy with limited off- target side effects. Over the span of two India Alliance Senior Fellowships we have evaluated drug resistance in acute promyelocytic leukemia (APL), a subtype of AML, and in AML. We have also observed and reported on a unique metabolic vulnerability in AML that can be targeted effectively by re-purposing arsenic trioxide (ATO) and artesunate (ART), an anti-malarial drug. The pre-clinical work has been completed. The key goal of this project is to translate this potentially efficacious and low-cost intervention into standard treatment algorithms for AML through an academic clinical trial and to develop additional novel strategies to predict response to this therapy.
Once we have completed the Phase I study we will move to the Phase II multi-centre RCT to compare the proposed low cost de-intensified intervention with a currently accepted standard of care therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Aged above 18 years of age Newly diagnosed de-novo acute myeloid leukaemia.
- •ECOG performance score above 2 Adequate renal function: Glomerular Filtration Rate above 60ml/min Adequate hepatobiliary function: Total bilirubin less than 2 x Upper limit normal Adequate cardiac function with no past history of ischaemic heart disease and normal ejection fraction Female participants of child bearing potential must have a negative pregnancy test less than 72 hours prior to initiating study intervention and agree to avoid pregnancy using adequate, medically approved contraceptive precautions for up to 6 weeks after the last dose of study treatment intervention Male participants with a partner of childbearing potential must agree to use adequate, medically approved contraceptive precautions during and for up to 6 weeks after the last dose of the study treatment intervention Patient able and willing to provide written, informed consent for the study.
排除标准
- •Contraindication to the use of arsenic trioxide or artesunate due to hypersensitivity or past history of adverse events with these agents, or any other medical contraindication to administer these drugs Pregnancy or lactation Male or female participants unwilling to use an effective method of birth control (either hormonal in the form of the contraceptive pill or barrier method of birth control accompanied by the use of a proprietary spermicidal foam/gel or film); or agreement of true abstinence from time consent is signed until 6 weeks after the last dose of study treatment intervention (i.e. withdrawal, calendar, ovulation, symptothermal and post ovulation methods are not considered acceptable methods)
- •Evidence of sepsis with hemodynamic compromise at diagnosis History of immunosuppression History of hearing or balance problems Any other malignant disease diagnosis within the preceding 2 years with the exception of non- melanomatous skin cancer and carcinoma in situ.
结局指标
主要结局
Best response rate (CR+iCR+MLFS) at end of 4 cycles of treatment
时间窗: At 30 days | At 60 days | At 180 days and | Once in a year
次要结局
- MRD negative rate by flowcytometry (less than 0.01% with a sensitivity of 10-5)(Event free survival defined as relapse or death due to any cause from date of)
研究者
Vikram Mathews
Christian Medical College Ranipet Campus