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

Primary Purpose

Neuroblastoma, Ewings Sarcoma, Osteogenic Sarcoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous dendritic cell vaccine with adjuvant
Sponsored by
University of Louisville
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring Neuroblastoma, Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma, synovial sarcoma, high-risk, relapsed, children

Eligibility Criteria

1 Year - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Louisville, Kosair Charities Pediatric Clinical Research Unit

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm study

Arm Description

Biological/Vaccine: Autologous dendritic cell vaccine with adjuvant

Outcomes

Primary Outcome Measures

Tolerance of study treatment
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
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
Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays.

Full Information

First Posted
November 15, 2010
Last Updated
May 8, 2017
Sponsor
University of Louisville
Collaborators
Solving Kids' Cancer
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1. Study Identification

Unique Protocol Identification Number
NCT01241162
Brief Title
Decitabine Followed by a Cancer Antigen Vaccine for Patients With Neuroblastoma and Sarcoma
Official Title
A Phase I Trial Combining Decitabine and Vaccine Therapy for Patients With Relapsed Neuroblastoma and Sarcoma.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Louisville
Collaborators
Solving Kids' Cancer

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Ewings Sarcoma, Osteogenic Sarcoma, Rhabdomyosarcoma, Synovial Sarcoma
Keywords
Neuroblastoma, Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma, synovial sarcoma, high-risk, relapsed, children

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single arm study
Arm Type
Experimental
Arm Description
Biological/Vaccine: Autologous dendritic cell vaccine with adjuvant
Intervention Type
Biological
Intervention Name(s)
Autologous dendritic cell vaccine with adjuvant
Other Intervention Name(s)
Decitabine (trade name Dacogen or 5-aza-2'-deoxycytidine/DAC, Hiltonol
Intervention Description
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
Primary Outcome Measure Information:
Title
Tolerance of study treatment
Description
Tolerance to DAC, at at least 50% dosing, and 3 of the 4 planned vaccinations during the first two cycles.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Tumor Response
Description
Assessment of tumor responses--complete or partial remission, stable disease, and disease progression--by CT/PET/MIBG or MRI after cycles 2 and 4.
Time Frame
2 years
Title
Immune Response
Description
Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
24 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth G Lucas, MD
Organizational Affiliation
University of Louisville, Kosairs Charities Pediatric Clinical Research Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville, Kosair Charities Pediatric Clinical Research Unit
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States

12. IPD Sharing Statement

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

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