Phase II Study of 5-azacytidine and Lintuzumab in Myelodysplastic Syndromes (MDS)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Complete Response Rate
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as lintuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving chemotherapy together with monoclonal antibodies may be a better way to block cancer growth.
PURPOSE: This phase II trial is studying the side effects and how well giving azacitidine together with lintuzumab works in treating patients with previously untreated myelodysplastic syndromes.
详细描述
OBJECTIVES:
Primary
- To determine the complete response rate of the combination of lintuzumab and azacitidine in patients with myelodysplastic syndromes.
Secondary
- To define the specific toxicities of this regimen.
- To determine the overall response rate.
- To determine the relationship between pretreatment expression of Syk and clinical response.
- To determine whether the investigational agents modulate Syk expression and to correlate drug-induced changes in Syk with response to treatment.
- To provide preliminary data on the biological activity of azacitidine as a demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation).
- To perform exploratory studies of azacitidine-triphosphate with global DNA methylation.
- To explore the biologic role of microRNA in determining clinical response to this regimen and achievement of the other pharmacodynamic endpoints.
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
- 未提供
排除标准
- •Patients who have had chemotherapy or radiotherapy within 6 months (for other cancers) prior to entering the study.
- •Patients receiving any other investigational agents or patients that have received other investigational agents within 1 month of enrollment.
- •Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease.
- •Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZA or lintuzumab that are not easily managed are excluded. Patients with hypersensitivity to mannitol are excluded.
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. As infection is a common feature of MDS, patients with active infection are permitted to enroll provided that the infection is under control. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- •Psychiatric conditions that prevent compliance with protocol or consent.
- •Pregnant women or women who are breastfeeding are excluded from this study.
- •HIV-positive patients on combination antiretroviral therapy are ineligible.
- •Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Patients with baseline fibrinogen <100mg/dL, or those with clinically significant disseminated intravascular coagulation, are excluded.
- •Patients who require ongoing therapeutic anticoagulation with warfarin, lovenox, or similar agent are excluded. This does not apply to patients on low dose prophylaxis therapy.
- •Patients who require ongoing clopidogrel therapy are excluded. In cases where clopidogrel use at screening is subsequently discontinued due to ongoing or future risk of drug and treatment related cytopenias, such patients will be eligible.
- •Patients with platelet <10,000/uL who are refractory to platelet transfusion are not eligible (must bump to at least >10,000/uL after transfusion)
- •Patients who have previously received lenalidomide or thalidomide are excluded.
研究组 & 干预措施
5-azacytidine and Lintuzumab
Cycle 1- 5-azacytidine (Vidaza, AZA) 75mg/m2 IV/SC(subcutaneous)daily on days 1-7.
Subsequent Cycles (cycles to be repeated every 28 days) AZA 75mg/m2 IV/SC daily on days 1-7.
干预措施: lintuzumab (Biological)
5-azacytidine and Lintuzumab
Cycle 1- 5-azacytidine (Vidaza, AZA) 75mg/m2 IV/SC(subcutaneous)daily on days 1-7.
Subsequent Cycles (cycles to be repeated every 28 days) AZA 75mg/m2 IV/SC daily on days 1-7.
干预措施: 5-azacytidine (Drug)
结局指标
主要结局
Complete Response Rate
时间窗: up to 5 years
Response to therapy was determined based on percentage of blasts in bone marrow, hematopoiesis, and requirement for supportive care (i.e., transfusions or cytokine growth factors). The modified International Working Group response criteria was used, based on Cheson, et al.
次要结局
- Overall Response Rate(up to 5 years)
- Determine the Relationship Between Pretreatment Expression of Syk and Clinical Response; to Determine Whether the Investigational Agents Modulate Syk Expression and Correlate Drug-induced Changes in Syk With Response to Treatment(up to 5 years)
- Explore the Biologic Role of microRNAs in Determining Clinical Response to the AZA Plus Lintuzumab Combination and Achievement of the Other Pharmacodynamic Endpoints(Up to 5 years)
- Perform Exploratory Studies of AZA-triphosphate With Global DNA Methylation(up to 5 years)
- Toxicities of the Combination(up to 5 years)
- Provide Preliminary Data on the Biological Activity of AZA as a Demethylating Agent (Changes in Target Gene Methylation and Gene Expression, DNMT1[Deoxyribonucleic Acid Methyltransferase 1 DNA Methyltransferase 1]Protein Expression, Global Methylation)(up to 5 years)
研究者
Alison Walker
Principal Investigator
Ohio State University Comprehensive Cancer Center