Bortezomib Plus Rituximab for EBV + Post Transplant Lymphoproliferative Disease (PTLD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 3
- 主要终点
- Overall Response Rate
研究概览
简要总结
Post transplant lymphoproliferative disease (PTLD) is a type of B-cell non-Hodgkin lymphoma that occurs in patients with weakened immune systems due to immunosuppressive medications taken after organ or stem cell transplantation. This is usually related to a virus called Epstein-Barr (EPV). Rituximab is a type of drug called an "antibody" that specifically destroys both normal and cancerous B-cells, and is commonly used for PTLD. Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) to treat multiple myeloma and a B-cell non-Hodgkin lymphoma called Mantle Cell Lymphoma, and shows significant activity in lymphoma cells caused by EBV. In this research study, we hope to learn if the addition of bortezomib to rituximab treatment can increase the rate of complete remissions and cures of PTLD after organ or stem cell transplant.
详细描述
- Both rituximab and bortezomib will be given to participants intravenously. Each cycle of treatment will consist of 21 days. Rituximab will be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles. Bortezomib will be given on Days 1, 4, 8 and 11 of every cycle. Participants will receive a maximum of 4 cycles.
- The following study procedures will be performed during each cycle throughout the study: Medical history review; Physical exam; Performance Status; Questionnaire; Blood draws and; PET/CT scans (After cycles 2, 4 and 6 only).
- After Cycle 4, if the study doctor feels the participant has had a complete response to treatment, then they will continue onto the Post-Treatment Surveillance period, which will consist of regular clinic visits over two years.
- However, if the study doctor feels the participant has had a partial response to treatment and that they may benefit from continuing, they will receive an additional two cycles of bortezomib and be given daily tablets of the antiviral drug valganciclovir to help further target EBV.
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 had a prior solid organ or allogeneic stem cell transplant.
- •Patients may be newly-diagnosed or relapsed after prior therapy
- •Patients must have histologically confirmed CD20+ B-cell PTLD diagnosed according to WHO criteria. PTLD may be characterized as early lesions, PTLD/polymorphic, PTLD/monomorphic, or PTLD/other, all of which are eligible for this trial. B-cell PTLD must be associated with EBV as demonstrated either by detection of EBV antigens in tumor samples, or by increased EBV quantitative viral load in serum.
- •Patients must have measurable disease
- •18 years of age or older
- •Estimated life expectancy of > 3 months
- •ECOG Performance status of 0, 1, or 2
- •Adequate organ and marrow function
- •Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
排除标准
- •Patients receiving any other study agents. Patients already on prophylactic doses of ganciclovir or valganciclovir because of a prior history of CMV infection or because of risk factors for CMV infection are eligible for the study and may continue CMV prophylaxis.
- •Patients with known brain metastases or central nervous system (CNS) involvement of their lymphoma.
- •Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, rituximab, ganciclovir or valgancyclovir.
- •Patients with Grade 2 or greater neuropathy within 14 days before enrollment.
- •Myocardial infarction within 6 months prior to enrollment or has 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 illness/social situations that would limit compliance with study requirements.
- •Pregnant or breastfeeding women
- •Individuals with a history of malignancy are ineligible except for those outlined in the protocol
- •Known HIV positive individuals
- •Active HBV infection may be included only if they are on appropriate anti-hepatitis B therapy and have an undetectable HBV viral load
- •Patient has received other investigational drugs within 14 days before enrollment
- •Prior bortezomib
研究组 & 干预措施
Rituximab plus Bortezomib
This is a single arm trial adding the new drug bortezomib to the standard drug rituximab
干预措施: bortezomib (Drug)
Rituximab plus Bortezomib
This is a single arm trial adding the new drug bortezomib to the standard drug rituximab
干预措施: rituximab (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: 4 months
Overall response rate includes both complete and partial responses assessed by PET/CT following completion of therapy. Response was evaluated using the International Working Group criteria for lymphoma response. The complete list of criteria used to evaluate response is too long to be detailed in the allotted space here, but response is defined more generally as: * Complete Response (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. * Partial Response (PR): ≥ 50% decrease in the sum of the products of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.
次要结局
- Complete Response Rate(4 Months)
- Six-Month Progression Free Survival(six months)
- Overall Survival(6 months, 1 year)
- Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load(baseline, 21, 42, 63, 84 days (end of cycles 1, 2, 3, 4))
- Treatment Related Toxicities(2 years)
研究者
Jeremy Abramson, MD
Director, Lymphoma Program
Massachusetts General Hospital