Decitabine Followed by a Cancer Antigen Vaccine for Patients With Neuroblastoma and Sarcoma - Full Text View

Purpose

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	Intervention	Phase
Neuroblastoma Ewings Sarcoma Osteogenic Sarcoma Rhabdomyosarcoma Synovial Sarcoma	Biological: Autologous dendritic cell vaccine with adjuvant	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Trial Combining Decitabine and Vaccine Therapy for Patients With Relapsed Neuroblastoma and Sarcoma.

Resource links provided by NLM:

Genetics Home Reference related topics: Ewing sarcoma neuroblastoma

MedlinePlus related topics: Neuroblastoma Soft Tissue Sarcoma

Drug Information available for: Decitabine

Genetic and Rare Diseases Information Center resources: Malignant Mesenchymal Tumor Soft Tissue Sarcoma Neuroblastoma Ewing Sarcoma Ewing's Family of Tumors Osteosarcoma Synovial Sarcoma Bone Cancer Neuroepithelioma

U.S. FDA Resources

Further study details as provided by University of Louisville:

Primary Outcome Measures:

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

Secondary Outcome Measures:

Tumor Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays.


Enrollment:	19
Study Start Date:	August 2010
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	August 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	1 Year to 24 Years (Child, Adult)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241162

Locations


United States, Kentucky
University of Louisville, Kosair Children's 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 Children Charities Pediatric Clinical Research Unit

More Information


Responsible Party:	Kenneth Lucas, Professor of Pediatrics, University of Louisville
ClinicalTrials.gov Identifier:	NCT01241162 History of Changes
Other Study ID Numbers:	34183
Study First Received:	November 15, 2010
Last Updated:	February 8, 2016
Health Authority:	United States: Food and Drug Administration

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 Vaccines Poly ICLC Decitabine Azacitidine Immunologic Factors Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

ClinicalTrials.gov processed this record on September 23, 2016