High Dose Therapy and Peripheral Blood Stem Cell Transplantation in HIV Related Non Hodgkin Lymphoma (NHL) at High Risk

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of an intensified first-line treatment, with conventional chemotherapy (CHOP) plus monoclonal antibody anti CD20, followed by high dose chemotherapy and PBSC transplantation in HIV-related aggressive non-Hodgkin lymphoma at high risk , according to the international prognostic index (IPI).

Detailed Description
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HIV associated NHL show particularly aggressive clinical features and a worse prognosis compared to the general population. The recent introduction of highly active antiretroviral therapy (HAART)has improved HIV positive patients' clinical conditions and reduced the risk of opportunistic infections, thus making HIV+ patients more similar to HIV- patients. Several studies have shown that the early use (as first line treatment) of high dose chemotherapy (HDT) with peripheral blood stem cell transplantation (PBSCT) is superior in the HIV negative setting to conventional dose chemotherapy, at least in patients with poor prognostic factors at diagnosis. Recently, several experiences have shown the feasibility, safety and efficacy of HDT and PBSCT, in association with HAART, as salvage therapy in HIV positive patients with lymphoma who maintain a chemosensitive disease after first-line treatment failure. It is rationale therefore to explore the use of this treatment strategy earlier, within the upfront treatment of HIV-associated lymphoma, in those patients with poor prognostic factors at diagnosis, according to the international prognostic score (IPI).

Official Title
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First Line Treatment in HIV-related Large Cell Non Hodgkin Lymphoma at High Risk, Including Early Consolidation With High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation

Conditions
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HIV-related Lymphoma, HIV Infections

Intervention / Treatment
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* Other: Rituximab and CHOP regimen + PBSCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV positivity Large cellhistology (DLBCL, Immunoblastic, Plasmablastic, Anaplastic lymphoma) Age 18-60 years Age-adjusted IPI 2-3 Ann Arbor stage I B-IV Written informed consent. Exclusion Criteria: Burkitt lymphoma Lymphoblastic lymphoma Primary effusion lymphoma Age-adjusted IPI 0-1 Performance Status (WHO) >2 (if not related to lymphoma) Inadequate cardiac function (V.E.F. < 50%) or clinically evident cardiac disease Inadequate pulmonary function (DLCO < 50% and/or O2 < 96%) Inadequate renal function (creatinine > 2 mg/dl) Inadequate liver function (AST/ALT > 3 ULN and/or PT < 70%, if not related to lymphoma) Inadequate marrow function (neutrophils < 1500/cmm; platelets < 100.000/cmm, if not related to lymphoma) Virologic failure to HAART (including at least one NRTI, one NNRTI and two PI) and/or CD4 count < 50/cmm. CNS or meningeal lymphoma Active opportunistic infections Pregnancy Other evolutive malignancy (except of localized non-melanoma skin cancer and in situ portio carcinoma) Any other condition that contraindicates this treatment program at discretion of physician HBsAg positivity with active viral replication (HBV-DNA positivity)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-CHOP + PBSCT<br>All patients will receive chemoimmunotherapy with Rituximab + CHOP regimen for 6 cycles followed by high dose cyclophosphamide and stem cell collection, then high dose therapy with BEAM conditioning regimen and peripheral blood stem cell transplantation | Other: Rituximab and CHOP regimen + PBSCT<br> <br> * Other names: melphalan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2-years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial and complete responses |  | Evaluation of response one month after peripheral blood transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, non hodgkin lymphoma, peripheral blood stem cell transplantation