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

NCT02332889 | Terminated Phase 1 Results DMC

• 1 other identifier: 14.0855
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

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.

Conditions

Gliomas; Medulloblastoma; Neuroectodermal Tumors, Primitive

Outcome Measures

Primary Outcomes (1)

• Tolerability (Number of Participants Without Adverse Events)

  20 weeks

Study Arms (1)

Decitabine/Vaccine Therapy

EXPERIMENTAL

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

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

Interventions

Vaccine (autologous dendritic cells) BIOLOGICAL

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/Vaccine Therapy

Decitabine and Hiltonol DRUG

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

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Louisville: lead

Study Sites (3)

Pediatric Hematology/Oncology University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Louisville, Kosair Children's Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Related Publications (1)

• Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.

  PMID: 34171339 DERIVED

MeSH Terms

Conditions

Glioma; Medulloblastoma; Neuroectodermal Tumors, Primitive

Interventions

Vaccines; Decitabine; poly ICLC

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Nancy Alsip
• Organization: University of Louisville

nancy.alsip@louisville.edu

5028522905

Study Officials

• Kenneth G Lucas, MD

  University of Louisville

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: January 7, 2015
• Study Start: April 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 4, 2018
• Results First Posted: April 30, 2018

Record last verified: 2018-05

Locations

US (3)