EPOCH and Rituximab to Treat Non-Hodgkin's Lymphoma in Patients With HIV Infection
EPOCH and Rituximab to Treat Non-Hodgkin's Lymphoma in Patients With HIV Infection
Background:

 -  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 CT and 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.
Background:

 This is a study to investigate in a preliminary fashion the feasibility of short course
 chemotherapy to participants with HIV-associated non-Hodgkin's lymphoma (HIV-NHL).

 This study will investigate if the paradigm for treatment can be successfully changed from a
 standard of 6 cycles to one cycle beyond complete remission with 6 total allowable cycles.

 Objective:

 To assess with 90 percent probability that at least 50 percent of participants treated with
 short-course EPOCH-R will be progression free at one year.

 Eligibility:

 Aggressive CD20 positive DLBCL.

 HIV+ serology.

 All stages (I-IV) of disease.

 ECOG Performance status 0-4.

 NHL previously untreated with cytotoxic chemotherapy.

 Age greater than or equal to 18 years.

 May not be pregnant or nursing.

 May not have received previous rituximab.

 Design:

 Participants will be treated every three weeks with a combination of EPOCH and rituximab for
 one cycle beyond CR/CRu by CT scan of all detectable tumors for a minimum of three and
 maximum of six cycles. Following cycle 2, CT, positron emission tomography scans (PET), and
 bone marrow biopsies (if initially positive) will be performed.

 At the conclusion of the study, we will estimate whether the number of cycles can be reduced
 using the paradigm. If the cumulative number of participants to relapse exceeds 25 percent by
 6 months, the study will be closed.

 Following the completion of chemotherapy, restaging will be performed 2 months following the
 end of treatment, then every 3 months for one year, every 6 months for one year, then every
 12 months until relapse, death, or loss to follow up.

 Antiretroviral therapy (ART) will be given concurrently with treatment regimen.

 To study the effects of treatment approach on parameters of HIV disease, measurements of CD4
 cells and viral loads will be made at baseline and at the completion of therapy, and then 2
 months following the end of treatment, and then every 3-6 months for a total of 24 months
 following chemotherapy.
-  INCLUSION CRITERIA:

 Aggressive CD20 positive Diffuse Large B-cell lymphoma confirmed by Laboratory of
 Pathology, NCI. Note: Participants with aggressive B-cell lymphoma of the plasmablastic
 lymphoma sub-type who do not have surface CD20 expression, are also eligible.

 HIV + serology.

 All stages (I-IV) of disease.

 ECOG Performance status 0-4

 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
 methotrexte (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

 -  AST and ALT less than or equal to 3x 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)

 -  ANC greater than or equal to 1000/mm(3)

 -  Platelet greater than or equal to 75,000/mm(3) (unless impairment due to 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
 SC-EPOCH-R.

 -  Examples include, but are not limited to:

 -  Severe AIDS-related wasting

 -  Sever intractable diarrhea

 -  Active inadequately treated opportunistic infection of the CNS

 -  Primary CNS lymphoma

 Primary CNS lymphoma