Clinical Trial: A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL

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

Official Title: A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL

Brief Summary: This is a pilot study using decitabine and vorinostat before and during chemotherapy with vincristine, dexamethasone, mitoxantrone, and peg-asparaginase in pediatric patients with acute lymphoblastic leukemia (ALL).

Detailed Summary: Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute lymphoblastic leukemia.
Sponsor: Therapeutic Advances in Childhood Leukemia Consortium

Current Primary Outcome: Number of participants with adverse events. [ Time Frame: 6 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Disease response rate after treatment. [ Time Frame: 6 weeks ]
  The study will assess whether the patient's acute lymphoblastic leukemia goes into remission after treatment.
• Gene-specific methylation profiles [ Time Frame: 2 years ]
  To assess the biologic activity of decitabine by comparing pre and post-treatment marrow samples for global and gene-specific methylation profiles using HELP and methylation-specific PCR.
• Global histone acetylation and histone modifications [ Time Frame: 2 years ]
  To assess the biological activity of vorinostat by comparing pre- and post-treatment blood and bone marrow samples for global histone acetylation (using acetyl-H3 Western blotting), and for gene-specific histone modifications (using H3K9/14Ac ChIP-chip and ChIP-qPCR).
• Gene expression profiles [ Time Frame: 2 years ]
  To determine the impact of combined epigenetic therapy on the expression of epigenetically-regulated genes by comparing pre and post-treatment marrow samples for gene expression profiles (using microarrays), and correlating these with the methylation and histone modification assays.

Original Secondary Outcome:

• Disease response rate after treatment. [ Time Frame: 6 weeks ]
  The study will assess whether the patient's acute lymphoblastic leukemia goes into remission after treatment.
• Gene-specific methylation profiles [ Time Frame: 2 years ]
  To assess the biologic activity of decitabine by comparing pre and post-treatment marrow samples for global and gene-specific methylation profiles using HELP and methylation-specific PCR.
• Global histone acetylation and histone modifications [ Time Frame: 2 years ]
  To assess the biological activity of vorinostat by comparing pre- and post-treatment blodd and bone marrow samples for global histone acetylation (using acetyl-H3 Western blotting), and for gene-specific histone modifications (using H3K9/14Ac ChIP-chip and ChIP-qPCR).
• Gene expression profiles [ Time Frame: 2 years ]
  To determine the impact of combined epigenetic therapy on the expression of epigenetically-regulated genes by comparing pre and post-treatment marrow samples for gene expression profiles (using microarrays), and correlating these with the methylation and histone modification assays.

Information By: Therapeutic Advances in Childhood Leukemia Consortium

Dates:
Date Received: November 29, 2011
Date Started: December 2011
Date Completion:
Last Updated: November 20, 2015
Last Verified: September 2015