LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)

Study Overview
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Brief Summary
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Main objective: To evaluate the applicability of the treatment: To evaluate the treatment toxicity according to the Common Terminology Criteria (CTC) version 3.0 of the National Cancer Institute (NCI). To evaluate opportunistic and non-opportunistic infections after 6 cycles of treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) administered every 14 days and highly active antiretroviral therapy (HAART) in patients with diffuse large B cell lymphoma (DLBCL) and HIV infection. To evaluate the adherence to the treatment with 6 cycles of R-CHOP considering the delays in the administration of the cycles and the reductions in the doses of chemotherapy (planned dose administered in predicted term). Secondary objectives: To evaluate the efficacy of the treatment in patients with DLBCL and HIV infection after 6 cycles of treatment with R-CHOP administered every 14 days (R-CHOP/14): To determine the global response and complete remission tax. To evaluate the duration of the response. To evaluate the probability of event-free survival in 5 years. To evaluate the probability of global survival in 5 years. To identify predictive factors of response after 6 cycles of treatment with R-CHOP administered every 14 days in patients with DLBCL and HIV infection. To evaluate the impact of the therapeutic combination of R-CHOP and HAART in the parameters of the HIV infection (HIV viral load and CD4+ lymphocyte count).

Detailed Description
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This is a clinical trial with a pharmaceutical drug used in the same conditions of authorization.

Official Title
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LINFOTARGAM: First-line Treatment With Dose-dense Chemotherapy Plus Rituximab (R-CHOP/14) and Highly Active Antiretroviral Therapy (HAART) in Patients With Diffuse Large B Cell Lymphoma (DLBCL) and Infection With the Human Immunodeficiency Virus (HIV)

Conditions
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HIV Infections, Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: R-CHOP
* Drug: Highly active antiretroviral therapy
* Drug: Central nervous system (CNS) prophylaxis
* Drug: Prophylaxis of opportunistic infections and support treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with HIV infection diagnosed with DLBCL in any stage (I-IV according to the Ann Arbor classification) not previously treated for the lymphoma. Patients with CD20-positive diffuse large B-cell lymphoma Aged from 18 to 70 years old Any score of International Prognostic Index. (It is also applicable in patients with non-Hodgkin lymphoma [NHL] infected with HIV.) ECOG performance status 0 to 3 Written informed consent Absolute neutrophil count > 1.5 x 10^9/L. Absence of synchronic or non-synchronic neoplasia with the exception of non-melanoma skin tumors or in situ cervical carcinoma. CD4+ lymphocyte count > 100/µL Exclusion Criteria: Patients with diffuse large B cell lymphoma previously treated. Patients with primary central nervous system lymphoma. Patients with Burkitt or Burkitt-like NHL. CD4+ lymphocyte count < 100/µL Opportunistic infections or other AIDS-related neoplasias in activity. Active drug-addiction. Pregnant or lactating women or adults of fertile age who do not use an effective contraceptive method. Patients with serious altered renal function (creatinine > 2.5 x upper limit of normal [ULN]) or hepatic [bilirubin, ALT or AST > 2.5 x ULN], except if the investigators suspect that they are caused by the disease. Cardiac insufficiency with ejection fraction < 40% Patients with serious psychiatric diseases that can interfere with their capacity to understand the study (including alcoholism or active drug-addiction). ECOG > 3 Patients with a known hypersensitivity to murine proteins or any other component of the study drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: R-CHOP|Cyclophosphamide 750 mg/m2 i.v. day 1 Adriamycin 50 mg/m2 i.v. day 1 Vincristine 1,4 mg/m2 i.v. day 1 Prednisone 100 mg i.v or oral. days 1-5.|
|Drug: Highly active antiretroviral therapy|Combined antiretroviral treatment (TARGA) wich include at lest 3 drugs. The combination should be accepted as an initial or rescue treatment.|
|Drug: Central nervous system (CNS) prophylaxis|methotrexate (12 mg) cytarabine (30 mg) hydrocortisone (20 mg)|
|Drug: Prophylaxis of opportunistic infections and support treatment|Pegfilgrastim|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment toxicity according to the CTC criteria (version 3.0) of the National Cancer Institute (NCI) |  | 6 months | 
| opportunistic and non-opportunistic infections rate after 6 cycles of treatment with R-CHOP administered every 14 days and HAART in patients with DLBCL and HIV infection |  | 6 months | 
| adherence to the treatment with 6 cycles of R-CHOP considering the delays in the administration of the cycles and the reductions in the doses of chemotherapy (planned dose administered in predicted term) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of the treatment in patients with DLBCL and HIV infection after 6 cycles of treatment with R-CHOP administered every 14 days |  | 1 year | 
| global response and complete remission rate |  | 1 year | 
| duration of the response |  | 5 years | 
| event-free survival probability in 5 years |  | 5 years | 
| global survival probability in 5 years |  | 5 years | 
| predictive factors of the response after 6 cycles of treatment with R-CHOP administered every 14 days in patients with DLBCL and HIV infection |  | 2 years | 
| impact of the therapeutic combination of R-CHOP and HAART in the parameters of the HIV infection (HIV viral load and CD4+ lymphocyte count) |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Diffuse large B cell lymphoma, R-CHOP, Highly active antiretroviral therapy, Treatment Experienced