Impact of Treatment Intensity on Survival, Quality of Life, and Resource Utilization in Medically Less Fit Adults With Acute Myeloid Leukemia and Analogous Myeloid Neoplasms: A Randomized Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Feasibility Defined as Proportion of Patients Willing to be Randomized to Either Intensive or Non-intensive Induction and Post Remission Chemotherapy
研究概览
简要总结
This randomized pilot trial studies how well higher or lower dose cladribine, cytarabine, and mitoxantrone work in treating medically less fit patients with newly diagnosed acute myeloid leukemia or myeloid neoplasm. Drugs used in chemotherapy, such as cladribine, cytarabine, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cladribine, cytarabine, and mitoxantrone at higher or lower dose may work better in treating patients with newly diagnosed acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the feasibility of randomizing medically less fit adults with newly diagnosed acute myeloid leukemia (AML) or analogous myeloid neoplasms to either intensive or non-intensive induction and post remission chemotherapy.
EXPLORATORY OBJECTIVES:
I. To evaluate the attitude of patients and physicians toward randomization and explore reasons for treatment preference.
II. To evaluate whether the ability to assess fitness for intensive chemotherapy can be improved by an augmented treatment-related mortality (TRM) score that includes additional (co-morbidity) factors, and to compare the ability of physicians and the prediction algorithm(s) to assess the likelihood of early death.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Diagnosis of untreated "high-grade" myeloid neoplasm (>= 10% myeloid blasts by morphology in bone marrow and/or peripheral blood) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; patients with acute leukemias of ambiguous lineage are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available
- •Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model
- •The use of hydroxyurea before enrollment is permitted; hydroxyurea should be discontinued prior to start of study treatment. Patients with symptoms/signs of leukostasis, white blood cell (WBC) > 100,000/uL, or acute symptoms felt related to their high-grade myeloid neoplasm can be treated with leukapheresis or may receive up to 1 dose of cytarabine (up to 500 mg/m^2) anytime prior to study day 1
- •Patients may have received treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm
- •Left ventricular ejection fraction (LVEF) >= 45%, assessed within 3 months prior to registration, e.g. by multigated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality
- •Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 4 weeks after the last dose of study drug
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment
- •Concomitant illness associated with a likely survival of < 1 year
- •Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable; patients with fever thought to be likely secondary to leukemia are eligible; known hypersensitivity to any study drug
- •Known hypersensitivity to any study drug used in this trial
- •Pregnancy or lactation
- •Concurrent treatment with any other anti-leukemia agent
研究组 & 干预措施
Arm II (lower-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm I (higher-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cladribine (Drug)
Arm I (higher-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cytarabine (Drug)
Arm I (higher-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Granulocyte Colony-Stimulating Factor (Biological)
Arm I (higher-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm I (higher-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm I (higher-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm II (lower-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cladribine (Drug)
Arm II (lower-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cytarabine (Drug)
Arm II (lower-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Granulocyte Colony-Stimulating Factor (Biological)
Arm II (lower-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm II (lower-dose)
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Feasibility Defined as Proportion of Patients Willing to be Randomized to Either Intensive or Non-intensive Induction and Post Remission Chemotherapy
时间窗: At end of enrollment
Randomizing patients to either intensive or non-intensive induction and post remission chemotherapy will be considered feasible if the true proportion of patients willing to be randomized is 60% or higher.
次要结局
未报告次要终点
研究者
Anna Halpern
Assistant Professor, Division of Hematology
University of Washington