Clinical Trials /

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

NCT00006436

Description:

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.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Plasmablastic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: EPOCH and Rituximab to Treat Non-Hodgkin's Lymphoma in Patients With HIV Infection
  • Official Title: Short-Course EPOCH-Rituximab in Untreated CD-20+ HIV-Associated Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 010030
  • SECONDARY ID: 01-C-0030
  • NCT ID: NCT00006436
  • NCT ALIAS: NCT00020384

Conditions

  • Lymphoma, AIDS-related
  • Lymphoma, Large B-Cell, Diffuse

Interventions

DrugSynonymsArms
Rituximab1
filgrastim1
EPOCH1

Purpose

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.

Detailed Description

      Background:

      This is a study to investigate in a preliminary fashion the feasibility of short course
      chemotherapy to patients 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 patients 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:

      Patients 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 patients 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.
    

Trial Arms

NameTypeDescriptionInterventions
1ExperimentalCombo chemo and biological therapy
  • Rituximab
  • filgrastim
  • EPOCH

Eligibility Criteria

        -  INCLUSION CRITERIA:

        Aggressive CD20 positive Diffuse Large B-cell lymphoma confirmed by Laboratory of
        Pathology, NCI. Note: Patients 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, patients 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 patients 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
             patients 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 patient 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
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:Time of progressive disease
Safety Issue:
Description:Disease progression as indicated by imaging scans and blood tests (CD4 cells and viral loads) at baseline, at the completion of therapy,2months following the end of treatment, and every 3-6 months (for a total of 24 months) following therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • AIDS
  • Malignancy
  • Antiretroviral
  • Chemotherapy
  • Monoclonal

Last Updated

November 20, 2019