Neoplasms

All Conditions

Rare Diseases

Glioma

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Decitabine

Vaccines

Poly ICLC

Antimetabolites

Enzyme Inhibitors

Interferons

Immunologic Factors

Biological/Vaccine: Vaccine (autologous dendritic cells) and Drug: Decitabine and Hiltonol

Prior to vaccination, DC will be thawed, washed once with normal saline containing 1% human serum albumin, and viability will be checked (must be \> 70%). Peptide pulsed DC will be placed in 1 ml tuberculin syringe(s) and transferred to the study physician for vaccination

Vaccine (autologous dendritic cells)

Patients will receive DAC at a dose of 10 mg/m2/d intravenously (IV) over one hour on days 1-5 of week 1. Hiltonol will be given intramuscularly at the same site immediately following vaccine

Decitabine and Hiltonol

Kenneth G Lucas, MD

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 NY-ESO-1, Melanoma Antigen Gene-A1 (MAGE-A1) and Melanoma Antigen Gene-A3 (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.

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 Major Histocompatibility Complex (MHC Class I and II ) molecules, which are needed for antigen presentation. Considering the ability of 5-aza-2-deoxycytidine (DAC) to facilitate the expression of cancer/testis (CT) antigens and major histocompatibility complex molecules (MHC) 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 Myelodysplastic syndromes (MDS) and Acute myeloid leukemia (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 dendritic cells (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 and consists 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 of doses given in previous studies. Vaccinations are spaced at weekly intervals, based on multiple previous studies in which this approach is taken, and the fact that in vitro re-stimulation of cytolytic T lymphocyte (CTL) generally occurs on a weekly basis. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is given days 1 through 5 during vaccine weeks, to minimize leukopenia from DAC and to help facilitate antigen presenting cell function. The adjuvant poly-interstitial Cajal-like cell (ICLC; Hiltonol) will be injected immediately after and adjacent to DC vaccine site to enhance DC maturation. We will accrue 10 patients with relapsed, refractory, or progressive pediatric brain tumors over a 3 year period. Cycles will repeat every five weeks, for two cycles. Patients who do not have disease progression after two cycles may receive an additional two cycles of therapy.

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

A Phase I/Pilot II Trial Combining Decitabine and Vaccine Therapy for Patients With Relapsed or Refractory Pediatric High Grade Gliomas, Medulloblastomas, and Central Nervous System Primitive Neuroectodermal Tumors (CNS PNETs)

University of Louisville

Biological/Vaccine: Vaccine (autologous dendritic cells) and Drug: Decitabine and Hiltonol

Vaccine (autologous dendritic cells): Prior to vaccination, DC will be thawed, washed once with normal saline containing 1% human serum albumin, and viability will be checked (must be \> 70%). Peptide pulsed DC will be placed in 1 ml tuberculin syringe(s) and transferred to the study physician for vaccination

Decitabine and Hiltonol: Patients will receive DAC at a dose of 10 mg/m2/d intravenously (IV) over one hour on days 1-5 of week 1. Hiltonol will be given intramuscularly at the same site immediately following vaccine

Decitabine/Vaccine Therapy

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Nancy Alsip

Tolerability (Number of Participants Without Adverse Events)

Biological/Vaccine: Vaccine (autologous dendritic cells) and Drug: Decitabine and Hiltonol

Vaccine (autologous dendritic cells \[DC\]): Prior to vaccination, DC will be thawed, washed once with normal saline containing 1% human serum albumin, and viability will be checked (must be \> 70%). Peptide pulsed DC will be placed in 1 ml tuberculin syringe(s) and transferred to the study physician for vaccination

Decitabine and Hiltonol: Patients will receive 5-aza-2-deoxycytidine (DAC) at a dose of 10 mg/m2/d intravenously (IV) over one hour on days 1-5 of week 1. Hiltonol will be given intramuscularly at the same site immediately following vaccine

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I/II: Decitabine/Vaccine Therapy in Relapsed/Refractory Pediatric High Grade Gliomas/Medulloblastomas/CNS PNETs	NCT02332889	Gliomas Medulloblastoma Neuroectodermal...	Vaccine (autolo... Decitabine and ...	2 Years - 25 Years	University of Louisville
Phase I/II: Decitabine/Vaccine Therapy in Relapsed/Refractory Pediatric High Grade Gliomas/Medulloblastomas/CNS PNETs	NCT02332889	Gliomas Medulloblastoma Neuroectodermal...	Vaccine (autolo... Decitabine and ...	2 Years - 25 Years	University of Louisville

Spots Global Cancer Trial Database for vaccine (autologous dendritic cells)