Phase II Study of Two Distinct Tailored Temozolomide Regimens for Patients With Acute Myeloid Leukemia Age > 60 Years and Poor Risk/Refractory Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Response Rate (CR + CRi + LFS)
研究概览
简要总结
Open-label, non-randomized, parallel assignment, phase 2 trial assessing the safety and efficacy of distinct temozolomide treatment regimens for patients with AML and poor prognosis
详细描述
This is a single institution phase 2 clinical trial evaluating the efficacy, safety, and tolerability of tailored temozolomide therapy for patients with acute myeloid leukemia (AML) and poor risk features.
Patients will be assigned to 1 of 2 parallel treatment groups based on their AGAT promoter region methylation status, as determined by PCR.
Patients achieving a complete remission after 1 to 2 cycles of chemotherapy will be eligible to receive up to an additional 5 cycles of temozolomide of 5 or 19 days, depending on the methylation status of the AGAT promoter (consolidation phase).
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed Acute Myeloid Leukemia, as defined by the WHO classification.
- •Patients must be considered unfit for conventional induction chemotherapy, unwilling to receive such treatment or have evidence of disease relapse or refractory disease.
- •For patients who have received no prior conventional chemotherapy, one of the following must be present:
- •Poor risk cytogenetics (complex abnormalities, deletions of chromosome 7 or 5, 11q23 abnormalities, inv[3])
- •Secondary leukemia (prior hematologic disorder or therapy-related leukemia).
- •Age > 60 years of age.
- •Life expectancy of greater than 3 months.
- •ECOG performance status greater than
- •Patients must have normal organ and marrow function as defined below:
- •Adequate hepatic function: Total bilirubin 1.5mg/dL, AST(SGOT)/ALT(SGPT) 2.5 X institutional upper limit of normal.
- •Adequate renal function: serum creatinine within normal institutional limits or Calculated creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Patients may not be receiving any other investigational agents.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or DTIC
- •History of gastrointestinal disease or significant bowel resection that could interfere with drug absorption.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Prior allogeneic stem cell transplantation.
- •Inability to swallow tablets
- •Prior radiation up to more than 25% of bone marrow.
研究组 & 干预措施
Methylated AGAT Promoter (Group 1)
Induction: 200 mg/m2/day oral Temozolomide x 7 days
干预措施: Temozolomide (Drug)
Un-Methylated AGAT Promoter (Group 2)
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
干预措施: Temozolomide (Drug)
结局指标
主要结局
Response Rate (CR + CRi + LFS)
时间窗: up to 2 months
Response determined per European LeukemiaNet response criteria: CR = bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0 x 10e9/L; platelet count \> 100 x 10e9/L; and independence of red cell transfusions. CRi = all CR criteria except for residual neutropenia (\< 1.0 x 10e9/L) or thrombocytopenia (\< 100 x 10e9/L)\]. Morphologic leukemia-free state (LFS) = bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; with no hematologic recovery required. Relapse = bone marrow blasts \>5%; reappearance of blasts in the blood; or development of extramedullary disease.
次要结局
- Toxicity Profile: Total Number of Drug-related Serious Adverse Events(12 months)
- Toxicity Profile: Individual Subjects With Drug-related SAEs(12 months)
研究者
Bruno C. Medeiros
PI
Stanford University