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

• ClinicalTrials.gov Identifier: NCT01241162
• Recruitment Status: Completed
• First Posted: November 16, 2010
• Last Update Posted: May 9, 2017
• Sponsor: University of Louisville
• Collaborator: Solving Kids' Cancer
• Information provided by (Responsible Party): University of Louisville

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neuroblastoma; Ewings Sarcoma; Osteogenic Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma	Biological: Autologous dendritic cell vaccine with adjuvant	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Trial Combining Decitabine and Vaccine Therapy for Patients With Relapsed Neuroblastoma and Sarcoma.
• Study Start Date: August 2010
• Actual Primary Completion Date: October 2016
• Actual Study Completion Date: October 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single arm study; Biological/Vaccine: Autologous dendritic cell vaccine with adjuvant	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; Other Names: Decitabine (trade name Dacogen or 5-aza-2'-deoxycytidine/DAC; Hiltonol

Outcome Measures

Primary Outcome Measures :

1. Tolerance of study treatment [ Time Frame: 2 years ]
   Tolerance to DAC, at at least 50% dosing, and 3 of the 4 planned vaccinations during the first two cycles.

Secondary Outcome Measures :

1. Tumor Response [ Time Frame: 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.
2. Immune Response [ Time Frame: 2 years ]
   Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays.

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 24 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Kentucky

University of Louisville, Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States, 40202

Sponsors and Collaborators

University of Louisville

Solving Kids' Cancer

Investigators

• Principal Investigator: Kenneth G Lucas, MD; University of Louisville, Kosairs Charities Pediatric Clinical Research Unit

More Information

• Responsible Party: University of Louisville
• ClinicalTrials.gov Identifier: NCT01241162
• Other Study ID Numbers: 34183
• First Posted: November 16, 2010
• Last Update Posted: May 9, 2017
• Last Verified: May 2017

Keywords provided by University of Louisville:

Neuroblastoma; Ewings sarcoma; osteogenic sarcoma; rhabdomyosarcoma; synovial sarcoma; high-risk; relapsed; children

Additional relevant MeSH terms:

Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Sarcoma, Ewing; Sarcoma, Synovial; Osteosarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Decitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors