The Highly Sensitized Patients: Effects of Rituximab and Mycophenolate Mofetil (MMF) On Anti-Human Leukocyte Antigen (HLA) Antibody Levels In Patients Awaiting Cadaveric Renal Transplant.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 主要终点
- The Number of Subjects Who Experience a Decrease in Their Panel of Reactive Antibodies (PRA) at 6 Months Post Rituximab Infusion.
研究概览
简要总结
This is a 12-month phase 2, prospective, open label study to evaluate the effect of rituximab with mycophenolate mofetil (MMF)on the PRA of 14 highly sensitized patients who just completed an 8 month trial of MMF treatment alone. PRA values obtained at study enrollment and at 6 and 12 months on combined therapy as well as the rates of transplant will be compared and evaluated using descriptive analysis.
详细描述
BACKGROUND: Patients who have been exposed to human tissue by prior transplants, blood transfusion or pregnancy may develop and maintain anti-bodies against these foreign human cells (SENSITIZATION). As a result of sensitization these patients are more likely to reject an organ donated from an individual who possesses a similar human cell marker (ANTIGENIC)profile. These sensitized patients will remain on the kidney transplant waiting list up to twice as long as those who are not pre-sensitized.
The Panel of Reactive Antibodies (PRA) is a test panel used to measure the patient reactivity to human leukocyte cell antigens (HLA). A PRA of 75% means the patient reacted to 75% of the antigens on the panel. A high PRA indicates that the subject already has antibodies and is highly SENSITIZED. Spontaneous decreases in PRA titers rarely occur. Thus the probability of transplantation in sensitized patients is significantly decreased.
RATIONALE for use of Rituximab:
By reducing specific B-cell populations Rituximab is currently used as a treatment in auto-immune diseases such as lupus erythematosus and rheumatoid arthritis and some cancers such as B-cell non-Hodgkin's lymphoma. It has been reported to have a potential roll in decreasing anti-human lymphocyte (HLA) antibodies post transplant. More studies are needed to assess its possible benefit among pre-transplant patients. Vierira et al. ["Rituxan for reduction of anti-HLA antibodies in patients awaiting renal transplantation", Am J Transplantation 2002;2:A870] reported on the use of rituximab in sensitized patients. Nine patients on dialysis with a PRA > 50% were treated with rituximab (n=3 per group) at 50, 150, or 375mg/m2. No significant change was seen in WBC, hemoglobin, platelet count, chemistry, liver enzymes or CMV IgG titers. At three days and 6 months after infusion there was a decline in the B cell count compared to pre-infusion levels. In 44%, a decline in PRA was seen. The patients receiving the higher doses had a larger decrement in antibody titers.
GENENTECH, INC. will provide Rituximab, labeled for investigational use. Rituximab is formulated for IV administration as a sterile product as a sterile, preservative-free liquid concentrate for intravenous (IV) administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age range 18 - 75, inclusive
- •Able and willing to give written informed consent and comply with the requirements of the study protocol
- •Outpatient status
- •Patients with a Panel of Reactive Antibodies (PRA) over 10% after an 8-month trial of MMF monotherapy
- •Patients with updated immunizations for tetanus, influenza, hepatitis B, pneumococcus
- •Patients with a negative purified protein derivative(PPD ) screen for tuberculosis (TB)within the last 6 months. If subject has a prior history of TB or positive PPD, documentation of adequate treatment is required.
- •Women who are of childbearing potential must have a negative serum pregnancy test prior to being enrolled in the study and agree to use a medically acceptable method of contraception throughout the study and for twelve months (1 year) after completion of treatment.
- •Men must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
- •Liver enzymes ALT and AST less than 2 times the normal limit.
排除标准
- •Active infection
- •Receipt of live vaccine within 4 weeks prior to first infusion.
- •Previous treatment with rituximab (MabThera® / Rituxan®)
- •History of multiple recurrent infections defined as more than 3 urinary tract infections, 2 episodes of pneumonia or 3 episodes of otitis/sinusitis in one year, or more than two dialysis line or peritoneal infections within one year.
- •Infection with hepatitis C virus (HCV) or hepatitis B virus(HBV) or human immunodeficiency virus (HIV), lack of documentation of treatment of a positive PPD, pregnant or breast-feeding, baseline leukopenia, white blood cell count (WBC) less than 4.0, thrombocytopenia (platelet count less than 100,000/mm) or difficult to treat anemia, a hematocrit chronically less than 32 on intravenous iron and EPO (erythropoietin) therapy, history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
- •Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- •History of psychiatric disorder
- •Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
结局指标
主要结局
The Number of Subjects Who Experience a Decrease in Their Panel of Reactive Antibodies (PRA) at 6 Months Post Rituximab Infusion.
时间窗: Month 6 from start of study
the number of subjects who experience a decrease in their Panel of Reactive Antibodies (PRA) at 6 months and 12 months post Rituximab infusion
次要结局
- The Number of Subjects Who Experience a Change From Baseline in Their Panel of Reactive Antibody (PRA) Titers at 12 Months Post Rituximab Infusion.(Month 12 from start of study)
- The Number of Subjects With a Negative Crossmatch at the Time of Transplant.(Month 12 from start of study)