Clinical Trial: Phase II of Chemotherapy for Relapsed Epstein Barr Virus Associated Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Study of Chemotherapy (Doxorubicin, Methotrexate and Leucovorin) in Combination With Antiviral-Based Therapy (Zidovudine + Hydroxyurea) for AIDS, Immunocompromised, or Immunocompetent Patient

Brief Summary: 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.

Detailed Summary:
Sponsor: University of Miami

Current Primary Outcome: Rate of Complete Response to Protocol Therapy [ Time Frame: Through Duration of Protocol Therapy, Up to six 21-day cycles (+/- 7 days) ]

Complete Response (CR) rate in study participants to protocol therapy. Response will be assessed via CT Scan and bone marrow aspirate/biopsy, if applicable. Complete response criteria include:

  • Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL;
  • All lymph nodes and tumor masses disappeared or regressed to normal size (≤ 1.5 cm in their greatest transverse diameters for nodes > 1.5 cm before therapy);
  • Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter (GTD) before treatment must have decreased to ≤ 1 cm in their GTD after treatment, or by more than 75% bin the sum of the products of the greatest diameters (SPD);
  • No new sites of disease.


Original Primary Outcome: Overall Survival Rate of Subjects [ Time Frame: 6 months ]

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


Current Secondary Outcome:

  • Rate of Overall Survival [ Time Frame: Up to 12 months ]
    Rate of overall survival of study participants. Overall survival (OS) will be measured from the date of initiation of study treatment until date of death from any cause. In the absence of death, the follow-up will be censored at date of last contact (censored observation).
  • Rate of Failure-Free Survival (FFS) [ Time Frame: Up to 12 months ]
    Rate of failure-free survival of study participants. Failure-free survival (FFS) will be measured from the date of treatment initiation until date of documented disease progression, relapse after response, or death from any cause. For patients alive and free of relapse or progression, follow-up time will be censored at the last documented date of failure-free status.
  • Rate of Toxicity Related to Protocol Therapy [ Time Frame: Through Duration of Protocol Therapy, Up to six 21-day cycles (+/- 7 days) ]
    Rate of adverse events, serious adverse events or other toxicities related to protocol therapy in study participants.
  • HIV Viral Load in Positive Subjects Before, During and After Protocol Therapy [ Time Frame: From Baseline Up to 1 Year Post-Therapy ]
    Measurement of HIV Viral Load in positive subjects before, during and after protocol therapy to assess the effect of protocol therapy on immune reconstitution or exhaustion.
  • T-Cell Subset Levels in Peripheral Blood Before, During and After Protocol Therapy [ Time Frame: From Baseline Up to 1 Year Post-Therapy ]
    Measurement of T-cell subset levels in peripheral blood before, during and after protocol therapy to assess the effect of protocol therapy on immune re-constitution or exhaustion.
  • EBV Viral Load in Peripheral Blood Before, During and after Protocol Therapy [ Time Frame: From Baseline Up to 1 year Post-Therapy ]
    Measurement of EBV viral load in peripheral blood in study participants before, after treatment, and during surveillance in order to correlate the presence of with tumor load and disease status.
  • EBV Reactivation in Circulating Peripheral Blood Memory B-cells Before and After Protocol Therapy. [ Time Frame: From Baseline Up to 1 year Post-Therapy ]
    Measurement of EBV reactivation in circulating peripheral blood memory B-cells before and after treatment with chemotherapy/ZDV in order to assess the drug effect on EBV latency.
  • Baseline Tumor EBV Gene Expression Profile in Study Participants [ Time Frame: Baseline ]
    Determine baseline tumor EBV gene expression profile to assess viral thymidine kinases. (BXLF1/vTK and BGLF4/PK), EBV latency pattern (I, II or III) and lytic phase.
  • Measurement of Immune Activation Markers and Inflammation in Peripheral Blood [ Time Frame: Through Duration of Response to Protocol Therapy Until Disease Progression, Up to 5 years ]
    Measurement of immune activation markers and inflammation in peripheral blood in response to treatment and EBV reactivation.


Original Secondary Outcome:

Information By: University of Miami

Dates:
Date Received: October 14, 2013
Date Started: April 21, 2009
Date Completion: April 2019
Last Updated: April 5, 2017
Last Verified: April 2017