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

• Status: Terminated
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Louisville
• Treatments: Azacitidine; Decitabine; Poly ICLC; Vaccines

Criteria

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.