Therapeutic Intensification of HIV-associated Non-Hodgkin's Lymphoma by Peripheral Blood Cell Transplantation Following Chemotherapy.
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.
Procedure: autologous peripheral blood cell transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Safety criteria defined as the occurrence of grades 3 or 4 adverse events in the 6 months following transplantation.
- 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
|Study Start Date:||February 2007|
|Study Completion Date:||October 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00432419
|Servide d'Immunologie Clinique|
|Creteil, France, 94010|
|Principal Investigator:||Yves LEVY, MD, PhD||Service d'Immunologie Clinique, Henri Mondor Hospital 94010 Creteil Cedex|
|Study Director:||Genevieve CHENE, MD, PhD||INSERM Unit 593, Bordeaux|