Ewings Sarcoma, Neuroblastoma, Osteogenic Sarcoma, Rhabdomyosarcoma, Synovial Sarcoma
Conditions
Keywords
Neuroblastoma, Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma, synovial sarcoma, high-risk, relapsed, children
Brief summary
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
For vaccine production, mature DC will be pulsed with overlapping peptides mixes derived from full-length NY-ESO-1, MAGE-A1, and MAGE-A3.
Interventions
BIOLOGICALAutologous dendritic cell vaccine with adjuvant
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
Sponsors
Solving Kids' Cancer
University of Louisville
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 24 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerance of study treatment | 2 years | Tolerance to DAC, at at least 50% dosing, and 3 of the 4 planned vaccinations during the first two cycles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | 2 years | Assessment of tumor responses--complete or partial remission, stable disease, and disease progression--by CT/PET/MIBG or MRI after cycles 2 and 4. |
| Immune Response | 2 years | Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays. |
Countries
United States
Outcome results
None listed