Phase I Study of Epigenetic Priming Using Decitabine With Induction Chemotherapy in Patients With Acute Myelogenous Leukemia (AML)

Weill Medical College of Cornell University1 个研究点分布在 1 个国家目标入组 30 人2007年7月

适应症Acute Myeloid Leukemia

概览

阶段: 1 期
干预措施: 未指定
疾病 / 适应症: Acute Myeloid Leukemia
发起方: Weill Medical College of Cornell University
入组人数: 30
试验地点: 1
主要终点: To establish the safety and expected toxicities of decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML
状态: 已完成
最后更新: 14年前

概览研究者入排标准结局指标研究点相似试验

概览

简要总结

This is an open label phase I study designed to explore the feasibility, safety and biologic activity of epigenetic priming with decitabine prior to standard cytarabine, daunorubicin induction chemotherapy in younger patients with less-than-favorable risk AML.

Primary Objective: To find an appropriate dose level for decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML.

Secondary Objectives:

To establish the safety and expected toxicities of decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML.
To establish the optimal dose schedule of decitabine required to broadly demethylate cytosine residues in genomic regulatory regions.
To investigate, in selected cases, the molecular and cellular consequences of decitabine-induced hypomethylation by a) establishing the extent and degree of hypomethylation at specific genomic loci required to reactivate the expression of repressed genes and by b) determining the effect of hypomethylation on the differentiation and/or apoptosis of leukemic blasts.

注册库

clinicaltrials.gov

开始日期

2007年7月

结束日期

2009年12月

最后更新

14年前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Weill Medical College of Cornell University

入排标准

入选标准

•Patients must have histologically or cytologically confirmed diagnosis of Acute Myelogenous Leukemia (AML)
•Patient is \>18 and ≤ 60 years of age.
•AML subgroup is associated with less-than-favorable risk as defined by:
•The absence of good risk molecular features: t(8;21), inv(16), t(16;16), or t(15;17) translocations identified by FISH or standard metaphase karyotyping or evidence for the corresponding fusion transcripts, AML1-ETO, CBFβ-SMMHC, or PML-RARα, as identified by RT-PCR or suggested by the FAB M3 phenotype;
•A history of an antecedent myelodysplastic syndrome;
•A history of an antecedent Philadelphia-chromosome negative myeloproliferative disorder (e.g., polycythemia vera, essential thrombocythemia, primary myelofibrosis);
•Treatment-related AML believed secondary to prior cytotoxic chemotherapy for an unrelated disease.
•Patient has adequate cardiac function as defined by:
•An echocardiogram or MUGA scan demonstrating an ejection fraction within normal limits.
•ECOG performance status \> =

排除标准

•AML with "good risk" molecular features: karyotype demonstrating the presence of t(8;21), inv(16), t(16;16), or t(15;17) translocations identified by FISH or standard metaphase karyotyping or evidence for the corresponding fusion transcripts, AML1-ETO, CBFβ-SMMHC, or PML-RARα, as identified by RT-PCR or suggested by the FAB M3 phenotype.
•Patient has a history of chronic myelogenous leukemia or has molecular evidence of the t(9;22) translocation by FISH, metaphase karyotype or RT-PCR for the BCR-ABL fusion transcript.
•Patient has received chemotherapy (other than hydroxyurea) or radiation within the 2 weeks prior to planned therapy on this study.
•Patient has an active second malignancy.
•Patient has a medical condition or illness considered by the Investigator to constitute an unwarranted high risk for investigational drug treatment.
•Patient has an uncontrolled serious infection.
•Patient is pregnant or nursing an infant.
•Patient has a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies.
•Patient has an inability or unwillingness, in the opinion of the Investigator, to comply with the protocol requirements.
•Patients with central nervous system (CNS) (or leptomeningeal) involvement by their AML may be considered for treatment at the Investigator's discretion and following discussion with the Medical Monitor, in order to allow for appropriate management.

结局指标

主要结局

To establish the safety and expected toxicities of decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML

时间窗: duration of study