Clinical Trial: Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma

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

Official Title: A Phase II Trial of Belinostat as Consolidation Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma

Brief Summary: The investigators propose to use Belinostat in combination with AZT as consolidation therapy for the treatment of ATLL.

Detailed Summary:

ATLL is an aggressive malignancy caused by HTLV-1. ATLL cannot be cured by conventional chemotherapy thus urging the development of new therapeutic strategies. HDAC inhibitors are broadly active anti-neoplastic agents that can be exploited for the treatment of ATLL as it has been demonstrated that pharmacologic inhibition of HDACs promotes acetylation of nucleosomes and chromatin unwinding at the HTLV-1 5' LTR, which results in transcription of the viral genome.

Belinostat, a potent pan HDAC inhibitor, causes H3 subunit acetylation and induces HTLV-1 Tax expression in cultured ATLL cells resulting in dose-dependent apoptosis. Further, Belinostat blocks constitutive expression of NF-κB, and increases apoptosis in the presence of AZT.

Sponsor: University of Miami

Current Primary Outcome:

• Rate of Participants achieving Complete Molecular Response (CMR) [ Time Frame: Up to 12 Months ]
  Rate of participants achieving Complete Molecular Response after receiving protocol therapy. Complete Molecular Response (CMR) is defined as no evidence of disease at any body sites AND the disappearance of malignant clone(s), as proven by negative T-cell receptor gene rearrangement studies of peripheral blood DNA.
• Rate of Participants Experiencing Treatment-Related Adverse Events [ Time Frame: Up to 30 Days after the last dose of protocol therapy ]
  Rate of participants experiencing adverse events/toxicities related to protocol therapy.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Rate of Participants Achieving Clinical Response [ Time Frame: Up to 12 months ]

  Rate of participants achieving complete response (CR) or partial response (PR) to protocol therapy. Response is assessed on the basis of clinical, radiologic, molecular and pathologic (i.e.

  bone marrow) criteria.

• Rate of Failure-Free Survival (FFS) [ Time Frame: Up to 12 months ]
  Rate of Failure-Free Survival in participants receiving protocol therapy. FFS is defined as the time from study treatment initiation until documented disease progression, relapse after response or death (by any cause, in the absence of progression). In the failure-free subjects, FFS will be censored at the last documented date of failure-free status.
• Rate of Overall Survival (OS) [ Time Frame: Up to 12 months ]
  Rate of overall survival (OS) in participants receiving protocol therapy. OS is defined as the elapsed time from study treatment initiation to death or date of censoring. Subjects alive or those lost to follow-up will be censored at the last date known to be alive.

Original Secondary Outcome: Same as current

Information By: University of Miami

Dates:
Date Received: April 10, 2016
Date Started: December 12, 2016
Date Completion: November 2021
Last Updated: April 5, 2017
Last Verified: April 2017