Phase II Study of Combination of Thymoglobulin, Cyclosporine, Methylprednisone, and Granulocyte Colony-stimulating Factor (GCSF) in Patients With Newly Diagnosed Aplastic Anemia or With Hypoplastic or Low/Intermediate-1 Risk Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Overall Response
研究概览
简要总结
The goal of this clinical research study is to learn if combining the drugs thymoglobulin, methylprednisolone, cyclosporine, and G-CSF (NeupogenTM or NeulastaTM ) can help to control severe aplastic anemia (AA) or hypoplastic myelodysplastic syndrome (MDS). The safety of this combination therapy will also be studied.
详细描述
Aplastic anemia is a condition that involves a low level of red blood cells (anemia), white blood cells, and platelets without evidence of another bone marrow disease. Anemia leads to fatigue, shortness of breath, and heart problems. Low platelet counts can lead to bruising and bleeding, and low white blood cell counts may cause an increased risk of infection, including pneumonia. Some of the treatment for AA includes transfusion, antibiotics and a combination of anti-thymocyte globulin (ATG) and cyclosporine with or without steroids, and growth factors such as G-CSF. For those who are eligible and have a donor, stem cell/bone marrow transplantation may be used.
MDS is a bone marrow disorder that usually affects older adults. Treatment of the bone marrow failure that accompanies MDS is usually with supportive care with red blood cell and platelet transfusions, antibiotics, and combinations of hematopoietic growth factors, which may partially improve blood cell counts.
It is often difficult to distinguish the hypoplastic variety of MDS from severe AA because both can result in bone marrow tests with very low cell count numbers. Earlier studies have shown that in some patients with the hypoplastic MDS, low blood counts respond to immunosuppressive treatment with ATG and cyclosporine. ATG is made from horse plasma. Thymoglobulin is a type of ATG made from rabbit plasma. Thymoglobulin has been successfully used to treat patients with AA who were previously treated with horse ATG but whose disease has returned. G-CSF is a growth factor that helps raise the white cell count after receiving chemotherapy. Methylprednisolone is a steroid that is commonly used in treating a number of medical conditions associated with people's abnormal immune response against themselves.
If you are found to be eligible to take part in this study, you will receive a combination of thymoglobulin, cyclosporine, G-CSF, and methylprednisolone. Treatment will be with thymoglobulin, which will be dosed depending on your age and weight. It will be given by vein over several hours once a day for a total of 5 days. You will receive the steroid methylprednisolone by vein before each dose of thymoglobulin to decrease the risk of developing allergic reactions to thymoglobulin. After 5 days of receiving methylprednisolone by vein, you will start taking it by mouth once a day at a decreasing dose over about 3 weeks.
The first 5 days of treatment will be given at M. D. Anderson but you will treated outside the hospital for the rest of the time unless complications develop.
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of severe aplastic anemia (bone marrow cellularity < 30%, with two of three peripheral counts at the time of initial presentation or currently low with absolute neutrophil count (ANC) < 500/mL, pre-transfusion platelet (PLT) < 20,000/mL, or pre-transfusion hemoglobin < 8 g/dL and presence of no other underlying disorder.
- •Diagnosis of MDS (World Health Organization) with bone marrow cellularity < 30%, with two of three peripheral counts at the time of initial presentation or currently low with ANC < 500/mL, pre-transfusion PLT < 20,000/mL, or pre-transfusion hemoglobin < 8 g/dL.
- •Patients with MDS who have received prior biological therapy (not chemotherapy) are eligible. Hypomethylating agents and histone deacetylase inhibitors are considered as biological therapy.
- •Age 15 or greater
- •Adequate renal function (creatinine less than or equal to 2.0 mg/dL) unless related to the disease
- •Adequate hepatic function (bilirubin less than or equal to 3.5 mg/dL) unless related to the disease
- •No other investigational therapy in the past 14 days
- •Able to sign consent form
- •Able to comply with the need for contraception (abstinence, condom, birth control pill, or other acceptable form of contraception) during the entire study period
- •Diagnosis of MDS (WHO) with bone marrow cellularity greater than 30%, with low or intermediate-1 risk by the International Prognostic Scoring System (IPSS) score, and requiring treatment (i.e. transfusion-dependent)
排除标准
- •Active and uncontrolled infection
- •HIV positive test
- •Pregnant or breast feeding
- •Active and uncontrolled medical illness (pulmonary, cardiac, neurological, or other) that in the opinion of treating physician would likely interfere with study treatment
研究组 & 干预措施
Thymoglobulin + Cyclosporin
Combination of Thymoglobulin 3.5 or 2.5 mg/kg/day intravenous (IV) for 5 days + Methylprednisone 1 mg/kg/day IV for 5 days, before each dose Thymoglobulin + Cyclosporin 5 mg/kg orally for 6 months following Thymoglobulin + Granulocyte - Colony Stimulating Factor (G-CSF) 5 microgram/kg subcutaneously daily up to 3 months
干预措施: Thymoglobulin (Drug)
Thymoglobulin + Cyclosporin
Combination of Thymoglobulin 3.5 or 2.5 mg/kg/day intravenous (IV) for 5 days + Methylprednisone 1 mg/kg/day IV for 5 days, before each dose Thymoglobulin + Cyclosporin 5 mg/kg orally for 6 months following Thymoglobulin + Granulocyte - Colony Stimulating Factor (G-CSF) 5 microgram/kg subcutaneously daily up to 3 months
干预措施: Cyclosporine (Drug)
Thymoglobulin + Cyclosporin
Combination of Thymoglobulin 3.5 or 2.5 mg/kg/day intravenous (IV) for 5 days + Methylprednisone 1 mg/kg/day IV for 5 days, before each dose Thymoglobulin + Cyclosporin 5 mg/kg orally for 6 months following Thymoglobulin + Granulocyte - Colony Stimulating Factor (G-CSF) 5 microgram/kg subcutaneously daily up to 3 months
干预措施: Methylprednisolone (Drug)
Thymoglobulin + Cyclosporin
Combination of Thymoglobulin 3.5 or 2.5 mg/kg/day intravenous (IV) for 5 days + Methylprednisone 1 mg/kg/day IV for 5 days, before each dose Thymoglobulin + Cyclosporin 5 mg/kg orally for 6 months following Thymoglobulin + Granulocyte - Colony Stimulating Factor (G-CSF) 5 microgram/kg subcutaneously daily up to 3 months
干预措施: G-CSF (Drug)
结局指标
主要结局
Overall Response
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Assessed first at 3 months on study, continuing monthly up to 3 years.
Complete response (CR) was defined as normalization of peripheral blood and bone marrow with \<5% blasts, a peripheral absolute neutrophil count (ANC) \>/= 1 \* 10\^9/l, hemoglobin \>/= 100g/l, and a platelet count \>/= \* 10\^9/l, Partial Response (PR) was defined as transfusion independence with a peripheral blood ANC \>=/ 0.05 \* 10\^9/l, a platelet count \>/= 20 \* 10\^9/l, and a hemoglobin \>/= 40 g/l. Hematologic improvement was defined as a clinically relevant increase in hemoglobin, platelets or absolute neutrophil count.
次要结局
未报告次要终点