Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma
Condition: AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Lymphoma, AIDS-Related
Intervention: cyclophosphamide; doxorubicin hydrochloride; vincristine sulfate; prednisone; lomustine; etoposide; cyclophosphamide; procarbazine hydrochloride; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Given PO; Given PO; Given PO; Given PO; Given PO; Correlative studies
Intervention MeSH terms: Prednisone; Cyclophosphamide; Lomustine; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Etoposide phosphate; Procarbazine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well intravenous (IV) chemotherapy or oral
      chemotherapy works in treating patients with previously untreated stage III-IV human
      immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma. Drugs used in chemotherapy,
      such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone,
      lomustine, etoposide, and procarbazine hydrochloride, work in different ways to stop the
      growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving
      more than one drug (combination chemotherapy) may kill more cancer cells
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to understand and the willingness to provide written informed consent to
             participate

          -  Adults, 18 years of age or older; date of birth should be determined based on the best
             possible information or source documentation available

          -  HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
             chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
             confirmed by a licensed Western blot or a second antibody test by a method other than
             the initial rapid HIV and/or E/CIA, or confirmed by HIV-1 antigen or plasma HIV-1
             ribonucleic acid (RNA) viral load > 1,000 copies/mL

               -  NOTE: the term "licensed" refers to a United States (U.S.) Food and Drug
                  Administration (FDA)-approved kit or for sites located in countries other than
                  the United States, a kit that has been certified or licensed by an oversight body
                  within that country and validated internally

               -  WHO (World Health Organization) and CDC (Centers for Disease Control and
                  Prevention) guidelines mandate that confirmation of the initial test result must
                  use a test that is different from the one used for the initial assessment; a
                  reactive initial rapid test should be confirmed by either another type of rapid
                  assay or an E/CIA that is based on a different antigen preparation and/or
                  different test principle (e.g., indirect versus competitive), or a Western blot
                  or a plasma HIV-1 RNA viral load

          -  Biopsy-proven, measurable or assessable systemic NHL that has been confirmed by an
             AIDS Malignancy Clinical Trial Consortium (AMC)-approved site pathologist; if a hard
             copy of the pathology report is unavailable at the time of enrollment, a verbal report
             by the pathologist confirming the diagnosis must be documented in the medical chart

          -  Pathology slides from tumor tissue obtained by surgical excision or core biopsy must
             be reviewed by the designated site pathologist, or backup pathologist, prior to study
             entry; confirmation of the diagnosis must be documented by the AMC-approved
             pathologist prior to study entry; please reference the AMC-068 Manual of Procedures
             (MOP) for further instructions on documenting the diagnosis; the site pathologist for
             NHL must be approved through the AMC's external quality assessment (EQA) process

          -  Participants must have fifteen blank(unstained) slides or a diagnostic tissue block
             must be available for central pathology review by the AMC Core Pathology Laboratory

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-3

          -  Participants must have an estimated life expectancy of > 6 weeks

          -  White blood cells (WBC) >= 3,000 cells/uL (3.0 x 10^9 L) or

          -  Absolute granulocytes >= 1500 cells/uL (1.5 x 10^9 L)

          -  Platelets >= 100,000 cells/uL (75 x 10^9 L)

          -  Hemoglobin > 8 g/dL (5.0 mmol/L)

          -  Patients may enroll with lower hematologic values, if bone marrow involvement is
             documented; in this case, patients should be transfused to hemoglobin > 8 g/dL

          -  Serum creatinine < 3.0 mg/dL (265.2 umol/L)

          -  Total bilirubin =< 1.5 institutional upper limit of normal (ULN), unless elevated
             secondary to lymphomatous involvement of liver or biliary system, or due to other HIV
             medications (e.g., indinavir, tenofovir, or atazanavir); if secondary to lymphomatous
             involvement, an initial upper limit of total bilirubin 5 mg/dL (85.5 uM/L) should be
             utilized - for direct bilirubin > 1.2 mg/dL (20.5 uM/L)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 institutional
             ULN (unless elevated secondary to lymphomatous involvement of the liver)

          -  Participants must have a lumbar puncture with negative cerebral spinal fluid cytology
             within 6 weeks prior to enrollment; participants must be without evidence for central
             nervous system (CNS) lymphoma on neurological exam and have no radiographic evidence
             (if radiographic studies are done) of CNS lymphoma (inclusive of parenchymal, vitreal,
             or leptomeningeal involvement)

          -  Participants must not have had any prior chemotherapy or radiation therapy and no more
             than 10 days of corticosteroids in the preceding 30 days prior to enrollment

          -  All participants must be prescribed combination antiretroviral therapy with the goal
             of virological suppression using an acceptable regimen that adheres to national
             guidelines for treatment of HIV infection; non-suppressed, treatment experienced
             patients, defined as patients with a viral load > 400 copies/mL who have been on
             antiretroviral therapy for more than 4 months can be enrolled if an alternative
             antiretroviral therapy (ART) regimen is available that includes at least two ART drugs
             that, in the opinion of the site investigator, are expected to have activity based on
             genotypic testing (if available) and treatment history; patients are not allowed to
             receive zidovudine (azidothymidine [AZT]) as part of concurrent chemotherapy and ART
             regimen, since it is myelosuppressive; zidovudine may be discontinued and substituted
             as clinically indicated prior to or at the time of enrollment.

          -  Participants of childbearing potential, defined as a sexually mature woman who: 1) has
             not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
             postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in
             the preceding 24 consecutive months), must have a pregnancy test within 7 days prior
             to enrollment and agree to use an effective form of contraception (e.g., barrier
             contraception, highly effective hormonal contraception)

          -  Participants are allowed to have an active infection(s) for which they are receiving
             drug treatment provided the clinical status is judged to be stable and survival is
             estimated to be at least 6 weeks

          -  Participants must, in the opinion of the investigatory, be capable of complying with
             the protocol

          -  Participants must be able to take oral medications

          -  Participants must have a CD4 count performed within 30 days of enrollment

        Exclusion Criteria:

          -  Inability to provide informed consent

          -  A medical or psychiatric illness that precludes ability to give informed consent or is
             likely to interfere with the ability to comply with the protocol stipulations

          -  Participants with circumstances that will not permit completion of the study or
             required follow-up; for instance, if travel to and from treatment site is an issue

          -  Pregnant or breastfeeding

          -  Inability to swallow oral medications