Decitabine Followed by a Cancer Antigen Vaccine for Patients With Neuroblastoma and Sarcoma

Study Overview
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Brief Summary
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This treatment study for relapsed high-risk neuroblastoma, Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma or synovial sarcoma involves an autologous cancer testis (CT) antigen specific dendritic cell (DC) vaccine preceded by decitabine as a demethylating chemotherapy.

Detailed Description
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For vaccine production, mature DC will be pulsed with overlapping peptides mixes derived from full-length NY-ESO-1, MAGE-A1, and MAGE-A3.

Official Title
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A Phase I Trial Combining Decitabine and Vaccine Therapy for Patients With Relapsed Neuroblastoma and Sarcoma.

Conditions
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Neuroblastoma, Ewings Sarcoma, Osteogenic Sarcoma, Rhabdomyosarcoma, Synovial Sarcoma

Intervention / Treatment
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* Biological: Autologous dendritic cell vaccine with adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of relapsed high-risk neuroblastoma,Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma, synovial sarcoma Patient may have gross tumor that has been treated with multi-agent chemotherapy prior study entry, but does not need to have gross tumor prior to study entry. Patients must have had a diagnosis of neuroblastoma or sarcoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines. Have received standard chemotherapy and/or SCT, and are at least 6 months post-transplant. Age: Patients must be 1 - < 25 years of age when registered on study. Organ Function Requirements: All patients must have adequate organ function defined as: Hematological Function: ANC ≥ 500; Platelet count ≥ 75. Renal Function: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR A maximum serum creatinine (mg/dL) based on age/gender as follows: 1YO M&F = 0.6, 2-5YO M&F = 0.8, 6-9YO M&F = 1, 10-12YO M&F = 1.2, 13-15YO M = 1.5, 13-15YO F = 1.4, 16+ M = 1.7, 16+ F = 1.4 Cardiac Function: Patient must have normal cardiac function documented by Ejection fraction (> 55%) documented by echocardiogram or radionuclide MUGA evaluation OR Fractional shortening (≥ 28%) documented by echocardiogram Liver Function: Total bilirubin ≤ 1.5 x normal for age, AND SGPT (ALT) and SGOT (AST) ≤ 3 x 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 performance scale > 70, ECOG < 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, HTLV-1 Ab, HTLV-2 Ab, RPR. Patient has a history of autoimmune disease, specifically inflammatory bowel disease, systemic lupus erythematosis, or rheumatoid arthritis. Patient is receiving concurrent systemic steroid therapy. Patient has a known systemic hypersensitivity to DAC, Hiltonol, or any vaccine component.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm study<br>Biological/Vaccine: Autologous dendritic cell vaccine with adjuvant | Biological: Autologous dendritic cell vaccine with adjuvant<br>* Week 1: Decitabine (DAC): 10 mg/m2/day IV (Mon-Fri) Weeks 2 and 3: Vaccine: 3-5 E6 peptide pulsed DC (Mon) Hiltonol applied topically to vaccine site before and after vaccination<br>* Other names: Hiltonol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance of study treatment | Tolerance to DAC, at at least 50% dosing, and 3 of the 4 planned vaccinations during the first two cycles. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | Assessment of tumor responses--complete or partial remission, stable disease, and disease progression--by CT/PET/MIBG or MRI after cycles 2 and 4. | 2 years | 
| Immune Response | Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroblastoma, Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma, synovial sarcoma, high-risk, relapsed, children