Back to resultsA Vaccine Study for High Risk Cancers
Primary Purpose
Neuroblastoma, Rhabdomyosarcoma, Osteogenic Sarcoma
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MAGE-A1, MAGE-A3, and NY-ESO-1 Vaccine
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring MAGE-A1, MAGE-A3, NY-ESO-1, antigen, vaccine, dendritic cells, immunohistochemistry, immunology
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Vaccine Intervention
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
The investigators will determine the safety of vaccine and imiquimod administration in these patients.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00944580
Brief Title
A Vaccine Study for High Risk Cancers
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 Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Withdrawn
Why Stopped
unexpectedly low screening results leading to poor accrual
Study Start Date
June 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Penn State University
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Rhabdomyosarcoma, Osteogenic Sarcoma
Keywords
MAGE-A1, MAGE-A3, NY-ESO-1, antigen, vaccine, dendritic cells, immunohistochemistry, immunology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vaccine Intervention
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
MAGE-A1, MAGE-A3, and NY-ESO-1 Vaccine
Intervention Description
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.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
The investigators will determine the safety of vaccine and imiquimod administration in these patients.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth G. Lucas, MD
Organizational Affiliation
Milton S. Hershey Medical Center
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
A Vaccine Study for High Risk Cancers
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