Phase I Investigation of the Feasibility of Combining 5-azacytidine With Highdose Cytarabine (HiDAC) and Mitoxantrone Chemotherapy in a Sequential Manner for Remission Induction in High-risk Acute Myelogenous Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Recommended phase II dose of azacitidine when combined with high-dose cytarabine and mitoxantrone hydrochloride, based on incidence of dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Toxicity Criteria, version 4
研究概览
简要总结
This phase I trial studies the side effects and best dose of azacitidine when given together with cytarabine and mitoxantrone hydrochloride in treating patients with high-risk acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, cytarabine, and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also help cytarabine and mitoxantrone hydrochloride work better by making the cancer cells more sensitive to the drugs
详细描述
PRIMARY OBJECTIVES:
I. To establish the recommended phase II dose of 5-azacytidine (azacitidine) when combined with high-dose cytarabine (HiDAC) and mitoxantrone (mitoxantrone hydrochloride) chemotherapy in high-risk acute myeloid leukemia (AML) patients.
SECONDARY OBJECTIVES:
I. To determine the complete remission (CR) rate following the use of induction chemotherapy regimen of 5-azacytidine followed by high-dose cytarabine (HiDAC) and mitoxantrone chemotherapy in high-risk AML patients.
II. To determine the toxicity of the combination regimen. III. To determine the disease-free survival (DFS) and overall survival (OS) of the patient population.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have one of the following disease characteristics:
- •Therapy-related myeloid neoplasm (t-MN) age >= 18 years
- •Patients must have received cytotoxic chemotherapy, radiation, or a drug known to affect the properties of deoxyribonucleic acid (DNA) or cell growth, prior to current diagnosis of therapy-related myeloid neoplasm (t-MN); this broad definition is meant to include any prior therapy with chemicals that affect DNA replication, DNA integrity, or DNA structure, or chemicals that alter cell growth; this includes traditional cytotoxic chemotherapy, newer immunologic agents that have been shown to have cytotoxic activities in addition to immunosuppressive functions, and other chemicals; note that patients with primary AML could be diagnosed with a t- MN if morphology/cytogenetic analysis clearly indicated that the second process is not a relapse of the original disease
- •AML arising from an antecedent hematological disorder age >= 18 years
- •De novo AML in patients age >= 60 years
- •Relapsed and/or refractory AML >= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
- •Male and female patients must use an effective contraceptive method during the study and for at least 6 months after study treatment
- •Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and must have recovered from clinically significant toxicities of these prior treatments
- •Ability to understand and willingness to sign the informed consent form
排除标准
- •Concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol
- •Diagnosis of acute promyelocytic leukemia (APL)
- •Use of investigational agents/any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea (note: for patients with hyperleukocytosis [white blood cell (WBC) > 20,000/uL], hydroxyurea [and leukapheresis, if clinically indicated] will be initiated and these patients will receive 5-azacytidine when the WBC count has decreased to =< 20,000/uL; hydroxyurea can be overlapped with 5-azacytidine in selected cases, after consultation with the study chair; hydroxyurea must be discontinued before the initiation of the HiDAC/mitoxantrone chemotherapy)
- •Prior treatment with 5-azacytidine followed immediately by HiDAC and mitoxantrone as proposed in this study (note: prior therapy with 5-azacytidine or decitabine or HiDAC or mitoxantrone would be allowed-in patients with relapsed/refractory disease- unless the prior therapy was identical to the schema/schedule proposed in this study)
- •Active second cancer other than specified; active cancer refers to cancer that requires systemic chemotherapy or biological therapy within 6 months of the study entry; patients who have received only hormonal therapy in the neoadjuvant or adjuvant setting in the past 6 months may participate in this study
- •Have any other severe concurrent disease, or have a history of serious organ dysfunction (e.g. uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, infection, psychiatric illness) that may in the judgment of the treating physician/ principal investigator place the patient at undue risk to undergo treatment
- •Pregnant or lactating patients
- •Any significant concurrent illness that would, in the judgment of the treating physician/principal investigator, compromise patient safety or compliance, or study participation
研究组 & 干预措施
Treatment (azacitidine, cytarabine, and mitoxantrone)
INDUCTION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10.
CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogeneic stem cell transplantation continue on to maintenance.
MAINTENANCE: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: azacitidine (Drug)
Treatment (azacitidine, cytarabine, and mitoxantrone)
INDUCTION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10.
CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogeneic stem cell transplantation continue on to maintenance.
MAINTENANCE: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: cytarabine (Drug)
Treatment (azacitidine, cytarabine, and mitoxantrone)
INDUCTION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10.
CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogeneic stem cell transplantation continue on to maintenance.
MAINTENANCE: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: mitoxantrone hydrochloride (Drug)
Treatment (azacitidine, cytarabine, and mitoxantrone)
INDUCTION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10.
CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogeneic stem cell transplantation continue on to maintenance.
MAINTENANCE: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Recommended phase II dose of azacitidine when combined with high-dose cytarabine and mitoxantrone hydrochloride, based on incidence of dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Toxicity Criteria, version 4
时间窗: 56 days
DLT defined as any grade 4 or greater non-hematologic toxicity (except transient \[less than 48 hours\] nausea/vomiting, transient \[less than 48 hours\] liver function test derangements) or a grade 3 non-hematological toxicity lasting more than 7 days. Persistent bone marrow aplasia (in the absence of bone marrow involvement with disease) lasting more than 56 days would also be regarded as a DLT.
次要结局
- Change in gene expression levels of topoisomerase II and deoxycytidine kinase in leukemic blasts pre-treatment and following therapy with azacitidine will be measured by real-time polymerase chain reaction (RT-PCR)(From baseline to day 56)