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

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01241162
• Other study ID #: 34183
• Status: Completed
• Phase: Phase 1
• First received: November 15, 2010
• Last updated: May 8, 2017
• Start date: August 2010
• Est. completion date: October 2016

Study information

• Verified date: May 2017
• Source: University of Louisville
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 24 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ewings Sarcoma
• Neuroblastoma
• Osteogenic Sarcoma
• Osteosarcoma
• Rhabdomyosarcoma
• Sarcoma
• Sarcoma, Ewing
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

Biological:
• Autologous 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

Locations

Country	Name	City	State
United States	University of Louisville, Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
University of Louisville	Solving Kids’ Cancer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Immune Response	Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays.	2 years