Clinical Trials /

Chemotherapy for Relapsed Epstein Barr Virus Associated Lymphoma

NCT01964755

Description:

By combining a variety of agents that potentiate Zidovudine (ZDV), the investigators hope to induce remission in this generally fatal disease. Most therapies for aggressive B cell lymphomas are based upon intensive chemotherapeutic regimens, expensive modalities (bone marrow transplant, Rituximab), or experimental approaches (gene therapy, cytotoxic T cell infusion) that are difficult to implement in heavily pre-treated patients. Therapy for relapsed aggressive B cell lymphomas is very poor. Even curable lymphomas such as Burkitt Lymphoma (BL) and Hodgkin lymphoma are extremely difficult to treat in relapse and/or after stem cell transplant failure. The investigators propose a novel therapeutic approach that exploits the presence of Epstein-Barr virus (EBV) in lymphomas; antiviral mediated suppression of NF-kB and disruption of viral latency.

Related Conditions:
  • Lymphoma
  • Post-Transplant Lymphoproliferative Disorder
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:Phase II of Chemotherapy for Relapsed Epstein Barr Virus Associated Lymphoma
  • Official Title:Phase II Study of Chemotherapy (Doxorubicin, Methotrexate and Leucovorin) in Combination With Antiviral-Based Therapy (Zidovudine + Hydroxyurea) for Relapsed Epstein Barr Virus Associated Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 20090166
  • NCT ID: NCT01964755

Trial Conditions

  • Epstein Barr Virus Associated Non Hodgkin's Lymphoma
  • Epstein Barr Virus Associated Hodgkin's Lymphoma
  • Post-Transplant Lymphoproliferative Disease

Trial Interventions

DrugSynonymsArms
DoxorubicinAdriamycinChemotherapy + Antiviral-Based Therapy
MethotrexateMethotrexate sodium, MTX, Mexate, Mexate-AQ, Folex, Folex PFS, Abitrexate, Rheumatrex, AmethoptetrinChemotherapy + Antiviral-Based Therapy
LeucovorinLeucovorin Calcium, Wellcovorin, Citrovorum Factor, Folinic Acid, 5-formyl tetrahydrofolate, LV, LCVChemotherapy + Antiviral-Based Therapy
ZidovudineRetrovir, AZT, ZDVChemotherapy + Antiviral-Based Therapy

Trial Purpose

By combining a variety of agents that potentiate Zidovudine (ZDV), the investigators hope to induce remission in this generally fatal disease. Most therapies for aggressive B cell lymphomas are based upon intensive chemotherapeutic regimens, expensive modalities (bone marrow transplant, Rituximab), or experimental approaches (gene therapy, cytotoxic T cell infusion) that are difficult to implement in heavily pre-treated patients. Therapy for relapsed aggressive B cell lymphomas is very poor. Even curable lymphomas such as Burkitt Lymphoma (BL) and Hodgkin lymphoma are extremely difficult to treat in relapse and/or after stem cell transplant failure. The investigators propose a novel therapeutic approach that exploits the presence of EBV in lymphomas; antiviral mediated suppression of NF-kB and disruption of viral latency.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Chemotherapy + Antiviral-Based TherapyExperimentalDoxorubicin, Methotrexate, and Leucovorin plus Zidovudine + Hydroxyurea All treatment will be administered on an inpatient basis. Treatment cycles will be given every 21-28 days, depending upon recovery from any hematologic or non-hematologic toxicity.
  • Doxorubicin
  • Methotrexate
  • Leucovorin
    • Zidovudine

    Eligibility Criteria

    Inclusion Criteria:

    - Any stage, histologically or cytologically documented intermediate to high grade relapsed or refractory non-Hodgkin's or Hodgkin's lymphoma. Patients with relapsed/refractory monomorphic (monoclonal) post-transplant lymphoproliferative disease (PTLD) are also eligible.

    - Tumors must be positive for EBV by EBER. This may be done either on the original tumor or the biopsy of relapsed disease (if performed). Biopsy of relapsed disease is desirable but not mandatory. If stains for LMP-1 done outside are positive, EBER does not need to be done.

    - All patients must have relapsed or progressed from at least one previous standard chemotherapy based regimen.

    - Measurable or non-measurable tumor parameter(s). Non-measurable tumor parameter(s) is defined as not having bi-dimensional measurements (e.g., gastric or marrow involvement), but can be followed for response by other diagnostic tests such as gallium scan, PET imaging and/or bone marrow biopsy.

    - Age >= 18 years.

    - Karnofsky performance status (KPS) >= 50%/Eastern Cooperative Oncology Group (ECOG) Performance Score 0, 1, 2.

    - Patients must have adequate end organ and bone marrow function as defined below:

    - Absolute neutrophil count >= 1,500 cells/mm3 and platelets >= 50,000 cells/dL unless cytopenias are secondary to lymphomatous involvement of bone marrow or due to HIV-related thrombocytopenia. All patients must be off colony stimulating factor therapy at least 24 hours prior to institution of Cycle 1 chemotherapy.

    - Adequate hepatic function: Serum glutamic-oxaloacetic transaminase (SGOT) <= 5 times the upper limit of normal. Total bilirubin <= 2.0 mg/dL (unless elevated secondary to lymphomatous involvement of liver or biliary system or due to other HIV medications [e.g., indinavir, tenofovir or atazanavir]). For bilirubin >= 3.0 mg/dL due to hepatic involvement, the initial dose of doxorubicin will be decreased by 50%.

    - Creatinine <= 2.0 mg/dL or creatinine clearance >= 60 mL/min unless due to renal involvement by lymphoma.

    - Concurrent radiation, with or without steroids, for emergency conditions secondary to lymphoma (CNS tumor, cord compression, etc.) will be permitted.

    - Patients who are HIV+ are eligible.

    - Females with childbearing potential must have a negative serum pregnancy test within 72 hours of entering into the study. Men and women must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study and for 6 months following the last study drug treatment.

    - Able to give consent.

    - Patients already receiving erythropoietin or G-CSF are eligible, although GF therapy must be discontinued at least 24 hours prior to receiving chemotherapy.

    Exclusion Criteria:

    - Concurrent active malignancies, with the exception of in situ carcinoma of the cervix, non-metastatic, non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy.

    - Patients who have previously received a cumulative dose of Doxorubicin of 350 mg/m2 or greater.

    - Myocardial infarction (MI) within 6 months prior to study entry, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe, uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiograph evidence of acute ischemic or active conduction system abnormalities.

    - Left Ventricular Ejection Fraction (LVEF) that is less than the lower institutional limits of normal as assessed by Multiple Gated Acquisition (MUGA) scan or echocardiogram within 6 weeks prior to registration.

    - Primary CNS lymphoma.

    - Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol.

    - Patients may not be receiving any other investigational agents.

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with mycobacterium avium will not be excluded.

    - Pregnant or breast-feeding women.

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Survival Rate of Subjects
    Time Frame:6 months
    Safety Issue:No
    Description:The primary objective of this phase II study is to determine the overall survival of patients with relapsed Epstein Barr Virus (EBV+) associated non-Hodgkin's and Hodgkin's lymphoma and post-transplant lymphoproliferative disease treated with high dose parenteral zidovudine (ZDV), oral hydroxyurea and combination chemotherapy with Doxorubicin, Methotrexate (MTX), and Leucovorin

    Secondary Outcome Measures

    Trial Keywords

    • EBV+
    • NHL
    • HL
    • Non Hodgkin's Lymphoma
    • Hodgkin's Lymphoma
    • Epstein Barr Virus
    • Epstein Barr Virus Associated Non Hodgkin's Lymphoma
    • Epstein Barr Virus Associated Hodgkin's Lymphoma
    • Post-Transplant Lymphoproliferative Disease