A Vaccine Study for High Risk Cancers

• ClinicalTrials.gov Identifier: NCT00944580
• Recruitment Status: Withdrawn
• First Posted: July 23, 2009
• Last Update Posted: November 24, 2017
• Sponsor: Penn State University
• Information provided by (Responsible Party): Penn State University

Study Description

Brief Summary:

The purpose of this study is to determine the safety and immunological effects of a vaccine for people diagnosed with high risk neuroblastoma, osteogenic sarcoma, and rhabdomyosarcoma. It is hypothesized that this vaccine could reduce the incidence of relapse.

Condition or disease	Intervention/treatment	Phase
Neuroblastoma; Rhabdomyosarcoma; Osteogenic Sarcoma	Biological: MAGE-A1, MAGE-A3, and NY-ESO-1 Vaccine	Phase 1

Detailed Description:

MAGE -A1, MAGE- A3, and NY-ESO-1 are antigens that can be found with significant frequency on neuroblastoma, rhabdomyosarcoma, and osteogenic sarcoma, three relatively common solid tumors that in some cases can be associated with a high risk for relapse. In this study each subject will be screened for the presence of these antigens, and an individualized vaccine will be developed and administered using the subject's own dendritic cells (DC).

This study consists of two phases: a screening phase and a treatment/vaccine phase. First, eligible individuals will be consented into the screening phase. Tumor specimens will be tested by immunohistochemistry or RT-PCR for the presence of MAGE- A1, MAGE- A3, and NY-ESO-1. Those testing positive for one or more antigen can be consented for the treatment phase of the study. Blood will be drawn for DC culture, and approximately one month later a series of three vaccines will be administered at two week intervals. Subjects will receive a topical medication called imiquimod to the vaccine site prior to and following each injection, to help immune cells travel into the area. Study participation occurs over 18 months and also involves periodic physical examinations and blood draws.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study to Determine the Immunologic Effects of a MAGE- A1, MAGE- A3, NY-ESO-1 Vaccine in Patients With High Risk Neuroblastoma, Osteogenic Sarcoma, and Rhabdomyosarcoma
• Study Start Date: June 2009
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: August 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vaccine Intervention; MAGE-A1, MAGE-A3, and NY-ESO-1 Vaccine: A regimen of three vaccines every two weeks. Each vaccine will contain 3,000,000-5,000,000 peptide pulsed dendritic cells. Imiquimod, a topical cream, will be applied to the vaccination site before and after each vaccination.	Biological: MAGE-A1, MAGE-A3, and NY-ESO-1 Vaccine; A regimen of three vaccines every two weeks. Each vaccine will contain 3,000,000-5,000,000 peptide pulsed dendritic cells. Imiquimod, a topical cream, will be applied to the vaccination site before and after each vaccination.

Outcome Measures

Primary Outcome Measures :

1. The primary objective is to determine if there is an amplification or new development of NY-ESO-1, MAGE-A1, or MAGE-A3 specific CD4+ or CD8+ T cells post-vaccination. [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. The investigators will determine the safety of vaccine and imiquimod administration in these patients. [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria for Screening Phase:

Patient 1 to 70 years of age with neuroblastoma, rhabdomyosarcoma, or osteogenic sarcoma, who have one or more of the following high risk features:

• Neuroblastoma:

  • Stage IV disease
  • Stage III disease with n-myc amplification

• Osteogenic sarcoma:

  • Presence of metastases
  • Elevated alkaline phosphatase or LDH at diagnosis
  • Primary tumor affecting the axial skeleton
  • Poor histopathological response after completion of pre-surgical chemotherapy (≥10% viable tumor)

• Rhabdomyosarcoma:

  • Stage IV disease
  • Alveolar histology
  • Positive tumor margins, with lymph node positivity

Inclusion Criteria for Vaccine Phase:

• Patient meets all screening criteria and tumor is positive for NY-ESO-1, MAGE- A1, or MAGE-A3 by immunohistochemistry or RT-PCR.
• Patients who are between 3 months and 2 years following the completion of therapy, and have achieved at least a very good partial response to primary therapy.
• No chemotherapy is planned for one month following the last vaccination.
• Bilirubin <2 mg/dL, and SGOT/SGPT <2.5 x normal
• Creatinine clearance > 50ml/min as estimated by patient's serum creatinine, weight, and age
• Room air pulse oximetry >94%
• Patient is not pregnant
• Male and female sexually active patients of reproductive who wish to participate must agree to use acceptable contraception
• Patient is not moribund and has a projected life expectancy >6 months
• Lansky performance scale > 70, ECOG < 2 (Appendix I)
• Potential subjects will be tested for HIV 1 and 2 antibodies, HTLV 1/2 antibodies, and for HIV 1, hepatitis C and hepatitis B virus by NAT testing. - -Subjects testing positive for any of these pathogens will be ineligible for vaccine.
• White blood cells ≥ 2.5 K/µL, Hemoglobin ≥ 8 g/dL, Hematocrit > 25%, and Platelets ≥ 70 K/µL
• Patient does not have central nervous system involvement.
• Patient does not a have a history of autoimmune disease, specifically inflammatory bowel disease, systemic lupus erythematosis, or rheumatoid arthritis
• Patient is not receiving concurrent systemic steroid therapy
• Patient does not have a known systemic hypersensitivity to imiquimod or any vaccine component

Contacts and Locations

Sponsors and Collaborators

Penn State University

Investigators

• Study Chair: Kenneth G. Lucas, MD; Milton S. Hershey Medical Center

More Information

• Responsible Party: Penn State University
• ClinicalTrials.gov Identifier: NCT00944580
• Other Study ID Numbers: IRB 30761; PSHCI 09-033
• First Posted: July 23, 2009
• Last Update Posted: November 24, 2017
• Last Verified: November 2017

Keywords provided by Penn State University:

MAGE-A1; MAGE-A3; NY-ESO-1; antigen; vaccine; dendritic cells; immunohistochemistry; immunology

Additional relevant MeSH terms:

Sarcoma; Neuroblastoma; Rhabdomyosarcoma; 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