EPOCH and Rituximab to Treat Non-Hodgkin's Lymphoma in Patients With HIV Infection
Condition: Lymphoma, AIDS-related; Lymphoma, Large B-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, AIDS-Related
Intervention: Rituximab; Filgrastim; EPOCH
Intervention description: 2 doses of rituximab every cycle: first dose on Day 1 and 2nd dose on Day 5; Filgrastim day 6 until absolute neutrophil count (ANC) reaches 5000 after the nadir, every cycle; combination chemotheray: EPOCH every 3 weeks for minimum of 3 cycles and max of 6 cycles
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Etoposide; Vincristine; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: AIDS; Malignancy; Antiretroviral; Chemotherapy; Monoclonal

Summary:

      Background:

        -  Human immunodeficiency virus (HIV)-infected patients have a weakened immune system, and
           chemotherapy, which is used to treat lymphoma, probably causes further damage to the
           immune system.

        -  Limiting the amount of immune damage due to chemotherapy might decrease the number of
           infections and the risk of developing cancer in the future in HIV-infected patients with
           non-Hodgkin's lymphoma.

      Objectives:

        -  To determine whether reducing the total amount of chemotherapy using a specific
           combination of drugs called EPOCH-R (etoposide, doxorubicin, vincristine,
           cyclophosphamide and rituximab) will rid the body of lymphoma quickly while decreasing
           the risk of infections and future cancers.

        -  To determine whether the lymphoma will remain undetectable for at least one year if
           treatment is stopped one cycle after the patient enters remission.

      Eligibility:

      -Patients with non-Hodgkin's lymphoma and HIV infection 4 years of age and older who have not
      been treated previously with rituximab or cytotoxic chemotherapy.

      Design:

        -  Patients receive EPOCH-R in 3-week treatment cycles for at least three and no more than
           six cycles.

        -  The lymphoma is evaluated using computed tomography (CT) and positron emission
           tomography (PET) scans at the end of treatment cycles 2 and 3. A bone marrow biopsy is
           repeated after cycle 2 if a biopsy was initially positive on screening for participation
           in the study.

        -  Anti-HIV therapy is stopped before chemotherapy begins and is restarted when EPOCH-R
           treatment ends.

        -  Patients are monitored for treatment response with blood tests and imaging scans at
           baseline, when treatment ends, 2 months after treatment ends and then every 3 to 6
           months for a total of 24 months following chemotherapy.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Aggressive B-lymphocyte antigen CD20 (CD20) positive Diffuse Large B-cell lymphoma
        confirmed by Laboratory of Pathology, National Cancer Institute (NCI). Note: Participants
        with aggressive B-cell lymphoma of the plasmablastic lymphoma sub-type who do not have
        surface CD20 expression, are also eligible.

        Human immunodeficiency virus (HIV) + serology.

        All stages (I-IV) of disease.

        Eastern Cooperative Oncology Group (ECOG) Performance status 0-4

        Non-Hodgkin's Lymphoma (NHL) previously untreated with cytotoxic chemotherapy; however,
        participants may be entered if they have had prior cyclophosphamide for an urgent problem
        at diagnosis (e.g., epidural cord compression, superior vena cava syndrome) and/or a single
        dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar
        puncture

        Age greater than or equal to 18 years

        Laboratory tests (unless impairment due to respective organ involvement by tumor):

          -  Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or
             equal to 50 ml/min

          -  Bilirubin less than 2.0 mg/dl, or total bilirubin less than or equal to 4.5 mg/dl with
             direct fraction less than or equal to 0.3 mg/dl in participants for whom these
             abnormalities are felt to be due to protease inhibitor therapy

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal
             to 3x upper limit of normal (ULN) (AST and ALT less than or equal to 6x ULN for
             participants on hyperalimentation for whom these abnormalities are felt to be due to
             the hyperalimentation)

          -  Absolute neutrophil count (ANC) greater than or equal to 1000/mm(3)

          -  Platelet greater than or equal to 75,000/mm(3) (unless impairment due to Immune
             thrombocytopenic purpura (ITP)

        Ability of participant to provide informed consent.

        EXCLUSION CRITERIA:

        Previous rituximab

        Pregnancy or nursing.

        - Doxorubicin, etoposide, vincristine and cyclophosphamide are teratogenic and may be
        excreted in milk.

        Current clinical heart failure or symptomatic ischemic heart disease.

        Serious underlying medical condition or infection other than HIV that would contraindicate
        subcutaneous (SC)-rituximab, etoposide phosphate, prednisone, vincristine sulfate,
        cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin (EPOCH-R).

          -  Examples include, but are not limited to:

          -  Severe Acquired immunodeficiency syndrome (AIDS)-related wasting

          -  Sever intractable diarrhea

          -  Active inadequately treated opportunistic infection of the central nervous system
             (CNS)

          -  Primary CNS lymphoma

        Primary CNS lymphoma