Therapeutic Intensification for HIV-associated Non-Hodgkin's Lymphoma by Autologous Transplantation of Either Unselected or CD34+-Selected Peripheral Blood Stem Cells, in Patients in First or Second Complete Remission. ANRS 131
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Safety criteria defined as the occurrence of grades 3 or 4 adverse events in the 6 months following transplantation.
研究概览
简要总结
Given the poor prognosis of HIV-associated non-Hodgkin's lymphoma (NHL) and it's still high incidence in HAART era, more intensive therapy is required in patients with initially severe stage of NHL or relapsing after first-line chemotherapy.
The purpose of this study is to evaluate the safety of an intensive chemotherapy followed by peripheral blood cell transplantation in these patients.
详细描述
Highly active antiretroviral therapy (HAART) has dramatically reduced mortality and morbidity of HIV-infected patients by decreasing the incidence of opportunistic infections and HIV-related malignancies such as Kaposi sarcoma. However, the frequency of NHL remains increased in these patients. Moreover, their prognostic remains poor comparing to HIV negative patients. This is mainly due to the type of NHL (aggressive B, and frequent stage IV) but also host factors such as immunodeficiency, co-infections (EBV, HHV8), and chemotherapy-HAART interactions. In the lack of new and significantly more efficient treatments, therapeutic intensification such as high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT), already tested in relapsed or partially responding HIV negative patients, could be an option in HAART controlled HIV+ patients with NHL, rather in first complete remission (CR) but with initially high International Prognosis Index (IPI above or equal to 2), or in second CR, whatever initial IPI. Positive selection CD34+ cells is an approach for depleting grafts of tumour cells and HIV DNA. However the delayed lymphocyte recovery following this process, may lead to increased incidence of opportunistic infections (OI) in HIV-infected patients. OI prophylaxis will be systematically associated.
Eligible patients will have peripheral blood stem cell (PBSC) mobilization and divided in two subgroups. Group A with 3-6 x 106 PBSC will not undergo CD34+ selection process and group B with more than 6 x 106 will undergo this process. The myeloablative conditioning process is the same in the two groups with total body irradiation before reinfusion of grafts.
Patients will be followed from week2 (W2) up to W60 with clinical and biological evaluations.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients between 18 and 55 years old at screening
- •Documented HIV-1 infection
- •Currently HAART-treated
- •Plasma HIV-RNA below 50 copies/ml at screening
- •Lymphocyte T CD4+ count above or equal to 100/mm3 at the NHL diagnosis
- •Histologically proven large cell NHL in first remission with classical poor prognostic factors (IPI above or equal to 2) or in second remission whatever IPI.
- •Biological criteria of eligibility for intensive therapeutic
- •Signed written informed consent
- •Patient protected by the social security of one of the European community countries.
排除标准
- •Burkitt NHL
- •Central nervous system NHL
- •Patients already treated by ASCT
- •Ongoing infectious disease
- •Psychiatric disease
- •Left ventricular ejection fraction < 25%
- •Creatinine clearance < 50 ml/min
- •Hepatic failure
- •Uncontrolled high blood pressure
- •Chronic hepatitis C or B
- •Participating in other trials.
结局指标
主要结局
Safety criteria defined as the occurrence of grades 3 or 4 adverse events in the 6 months following transplantation.
次要结局
- Evaluation of:
- HIV RNA
- HIV DNA
- Percentage and absolute count of CD3, CD4+ and CD8+ lymphocytes
- Lymphocyte phenotypes and functions
- TREC analysis
- Immune reconstitution in vivo
- Duration of aplasia