Therapeutic Intensification of HIV-associated Non-Hodgkin's Lymphoma by Peripheral Blood Cell Transplantation Following Chemotherapy.

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

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

Conditions
-----------------
HIV Infections, Lymphoma, Non-Hodgkin

Intervention / Treatment
-----------------
* Procedure: autologous peripheral blood cell transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: autologous peripheral blood cell transplantation|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety criteria defined as the occurrence of grades 3 or 4 adverse events in the 6 months following transplantation. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Non-Hodgkin's lymphoma, Peripheral blood stem cells transplantation