We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02332889
Recruitment Status : Terminated (Transition to a different immunotherapy strategy in the future at our institution)
First Posted : January 7, 2015
Results First Posted : April 30, 2018
Last Update Posted : May 4, 2018
Information provided by (Responsible Party):
University of Louisville

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 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.

Condition or disease Intervention/treatment Phase
Gliomas Medulloblastoma Neuroectodermal Tumors, Primitive Biological: Vaccine (autologous dendritic cells) Drug: Decitabine and Hiltonol Phase 1 Phase 2

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Central Nervous System Primitive Neuroectodermal Tumors (CNS PNETs)
Study Start Date : April 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines
Drug Information available for: Decitabine

Arm Intervention/treatment
Experimental: Decitabine/Vaccine Therapy
Biological/Vaccine: Vaccine (autologous dendritic cells) and Drug: Decitabine and Hiltonol
Biological: 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

Drug: 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

Primary Outcome Measures :
  1. Tolerability (Number of Participants Without Adverse Events) [ Time Frame: 20 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   2 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Criteria for enrollment:

  • Relapsed medulloblastoma, CNS PNET, or high grade glioma. Confirmatory biopsy is required at time of initial diagnosis.
  • Because of rapid clinical progression and decline at time of relapse in patients with grade IV gliomas and diffuse intrinsic pontine gliomas (DIPGs), and the 4-6 weeks required to develop vaccine, patients with these tumors will be eligible to enroll and have DCs harvested and stored at the time of diagnosis, but will not be treated with vaccine until time of relapse.
  • Age: Patients must be 2 to 25 years of age.

Criteria for treatment:

  • The patient must have experienced relapsed, progressive, or refractory disease.
  • The patient may have gross tumor that has been treated with chemotherapy or radiation prior to study treatment.
  • The patient must have received standard therapy for their tumor.
  • The patient must be at least 90 days from primary radiotherapy.
  • Hematologic Function: absolute neutrophil (ANC): 1000/uL; Platelet count: 75,000/uL.
  • Renal Function: Creatinine clearance or radioisotope glomerular filtration rate (GFR) 70ml/min/1.73 m2 .
  • Cardiac Function: Patient must have normal cardiac function documented by:
  • Ejection fraction (>55%) documented by echocardiogram or radionuclide multigated acquisition (MUGA) scan evaluation OR
  • Fractional shortening (≥28%) documented by echocardiogram
  • Liver Function: Total bilirubin 1.5x normal for age, and serum glutamate pyruvate transaminase (SGPT (ALT)) and serum glutamate oxaloacetate transaminase (SGOT (AST)) 3x normal for age.
  • Room air pulse oximetry >94%.
  • Male and female sexually active patients of reproductive age who wish to participate must agree to use acceptable contraception.
  • Lansky/Karnofsky performance scale > 50, electrocorticogram (ECOG) < or = 2 (Appendix I).

Exclusion Criteria:

  • Patient is pregnant.
  • Patients with a positive result for any of the following diagnostic tests: Hep B Ag, Hep B Core Ab, Hep C Ab, HIV-1 Ab, HIV-2 Ab, human T-cell leukemia virus (HTLV-1 Ab), HTLV-2 Ab, rapid plasma reagin (RPR).
  • Patient has a history of autoimmune disease, specifically inflammatory bowel disease, systemic lupus erythematosis, or rheumatoid arthritis.
  • Patient is receiving high doses of systemic corticosteroids or concurrent chemotherapy at the time of beginning study treatment. (Maximum dose of dexamethasone allowed is 0.1mg/kg/day not to exceed 4mg/day.)
  • Patient has a known systemic hypersensitivity to DAC, Hiltonol, or any vaccine component.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02332889

Layout table for location information
United States, Kentucky
Pediatric Hematology/Oncology University of Louisville
Louisville, Kentucky, United States, 40202
University of Louisville, Kosair Children's Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
University of Louisville
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
University of Louisville
Layout table for investigator information
Principal Investigator: Kenneth G Lucas, MD University of Louisville
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Louisville
ClinicalTrials.gov Identifier: NCT02332889    
Other Study ID Numbers: 14.0855
First Posted: January 7, 2015    Key Record Dates
Results First Posted: April 30, 2018
Last Update Posted: May 4, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs