Clinical Trial: Phase I/II: Decitabine/Vaccine Therapy in Relapsed/Refractory Pediatric High Grade Gliomas/Medulloblastomas/CNS PNETs

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

Official Title: A Phase I/Pilot II Trial Combining Decitabine and Vaccine Therapy for Patients With Relapsed or Refractory Pediatric High Grade Gliomas, Medulloblastomas, and CNS PNETs

Brief Summary: The main purpose of this study is to determine the safety of using the combination of decitabine and a cancer vaccine plus Hiltonol. The vaccine will be made from the subject's blood cells and is designed to interact in the subject's body with cells that are programmed to fight specific tumor proteins called NY-ESO-1, MAGE-A1 and MAGE-A3. The decitabine will be given to increase the amount and activity of these cancer proteins on the surface of tumor cells to increase the possibility that the vaccine will stimulate cells to act against the tumor cells. Subjects will be assessed to determine how these tumors respond to the treatment.

Detailed Summary:

One of the challenges of the practical application of immunotherapy for brain tumors is the lack of expression of tumor antigens as well as the down-regulation of MHC Class I and II molecules, which are needed for antigen presentation. Considering the ability of DAC to facilitate the expression of CT antigens and MHC molecules and the fact that it has good blood brain barrier penetration, it is reasonable to test this approach in a vaccine study for patients who have experienced disease recurrence. The use of a combined approach to tumor immunotherapy - antigen upregulation followed by vaccination - has not been studied in this patient population, and there is a strong biologic rationale for this strategy.

Patients with pediatric brain tumors (medulloblastoma, CNS PNET, high grade glioma) who have experienced disease relapse or progressive refractory disease will be eligible. Each cycle will consist of DAC at low dose administered over a 5 day period, followed by two weekly vaccinations consisting of autologous dendritic cells pulsed with pooled, overlapping peptide mixes derived from full-length MAGE-A1, MAGE-A3, and NY-ESO-1. This dose of DAC is lower than all previously reported doses that have been safely administered in adult patients with MDS and AML, and was used in a previous protocol for relapsed and refractory pediatric neuroblastoma and sarcomas. A novel way of stimulating CD4 and CD8 antigen specific T cells is to use a DC vaccine approach in which the cells are pulsed with overlapping peptides derived from these antigens, so that patients from several different HLA backgrounds can be enrolled. Overlapping peptide mixes derived from full-length NY-ESO-1, MAGE-A1, or MAGE-A3 have been acquired from JPT Peptide Technologies, consisting of 15-mers, with 11 amino acid overlap. The number of DC given in our study (8-10 x 106 peptide pulsed DC) is within the range o
Sponsor: University of Louisville

Current Primary Outcome:

  • Tolerability (absence of adverse events) of the treatment regimen [ Time Frame: 20 weeks ]
  • Monitor the frequency of non-hematologic toxicity of the treatment regimen [ Time Frame: 20 weeks ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Determine any amplification or new development of NY-ESO-1, MAGE-A1, or MAGE-A3 specific T cells and/or antibodies [ Time Frame: 20 weeks ]
  • Describe changes in T cell and antibody responses [ Time Frame: 20 weeks ]
  • Describe response to therapy [ Time Frame: 20 weeks ]


Original Secondary Outcome: Same as current

Information By: University of Louisville

Dates:
Date Received: October 20, 2014
Date Started: April 2015
Date Completion:
Last Updated: May 8, 2017
Last Verified: May 2017