Clinical Trial: Zidovudine, Interferon Alfa-2b, and PEG-Interferon Alfa-2b in Treating Patients With Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia/Lymphoma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Prospective Study of the Molecular Characteristics of Sensitive and Resistant Disease in Patients With HTLV-I Associated Adult T Cell Leukemia Treated With Zidovudine (AZT

Brief Summary:

RATIONALE: Human T-cell lymphotropic virus type 1 can cause cancer. Zidovudine is an antiviral drug that acts against the human T-cell lymphotropic virus type 1. Giving zidovudine, interferon alfa-2b, and PEG-interferon alfa-2b together may stimulate the immune system and slow down or keep the cancer cell from growing.

PURPOSE: This clinical trial is studying how well giving zidovudine together with interferon alfa-2b and PEG-interferon alfa-2b works in treating patients with human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma.


Detailed Summary:

OBJECTIVES:

Primary

  • To investigate whether the lack of IRF-4 and/or c-Rel is associated with response (complete response or partial response) to zidovudine, recombinant interferon alfa-2b, and PEG-interferon alfa-2b therapy in patients with human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL).
  • To analyze, in responders, the presence of any remaining detectable clones of ATLL (minimal residual disease) at 3 and 6 months of maintained remission on antivirals and at one-year post-initiation of therapy in order to determine whether this represents persistence of the original tumor clone or another variant.
  • To analyze clones from patients who relapse to determine whether antiviral escape is associated with expression of IRF-4, c-Rel, or other molecular events (p53, p16 mutations) including expansion of novel clones.
  • To investigate whether zidovudine functions as an inhibitor of NF-κB in vivo by analyzing serially collected leukemic samples during the first 48 hours of treatment with zidovudine alone.
  • To determine the effect of valproic acid therapy on persistent clonal disease in patients in complete or stable partial remission.

Secondary

  • To determine the failure-free survival and overall survival of these patients.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive zidovudine IV twice daily on days 1-14, and recombinant int
    Sponsor: University of Miami

    Current Primary Outcome:

    • To Investigate Whether the Lack of IRF-4 and/or c-Rel is Associated With Response (CR or PR) to Zidovudine (AZT) and IFN Alpha-2b Therapy. [ Time Frame: 3, 6 and 12 months. ]
    • Presence of Minimal Residual Disease at 3 and 6 Months of Maintained Remission and at 1 Year Post Initiation of Therapy [ Time Frame: 3, 6 and 12 months. ]
    • To Analyze Clones From Patients Who Relapse to Determine Whether Antiviral Escape is Associated With Expression of IRF-4, c-Rel or Other Molecular Events (p53, p16 Mutations) Including Expansion of Novel Clones. [ Time Frame: 3, 6 and 12 months. ]
    • To Investigate Whether AZT Functions as an Inhibitor of NF-kB in Vivo by Analyzing Serially Collected Leukemic Samples During the First 48 Hours of Treatment With AZT Only. [ Time Frame: 3, 6 and 12 months. ]
    • Number of Patients Who Achieved Complete Response or Partial Response According to Molecular Response Criteria [ Time Frame: 3, 6 and 12 months. ]
      To determine the effect of valproic acid therapy on persistent clonal disease in patients in complete or stable partial remission.


    Original Primary Outcome:

    • Association between the lack of IRF-4 and/or c-Rel and response
    • Presence of Minimal Residual Disease at 3 and 6 Months of Maintained Remission and at 1 Year Post Initiation of Therapy
    • Association between antiviral escape and expression of IRF-4, c-Rel, or other molecular events
    • Function of zidovudine as an inhibitor of NF-κB
    • Effect of valproic acid therapy on persistent clonal disease


    Current Secondary Outcome:

    • Failure-free Survival [ Time Frame: measured from the date of treatment initiation until date of documented disease progression, relapse after response, or death from any cause. ]
      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.
    • Overall Survival [ Time Frame: Measured from the date of initiation of study treatment until date of death from any cause. ]
      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).


    Original Secondary Outcome: Failure-free and overall survival

    Information By: University of Miami

    Dates:
    Date Received: February 28, 2009
    Date Started: November 2007
    Date Completion:
    Last Updated: November 23, 2015
    Last Verified: November 2015