This research clinical trial is studying the creation and administration of GVAX, an irradiated GM-CSF secreting, autologous neuroblastoma cell vaccine (GVAX) in combination with nivolumab and ipilimumab as a possible treatment for neuroblastoma. The names of the study drugs involved in this study are: * GVAX Vaccine, an immunotherapy developed from surgically removed tumor tissue * Nivolumab * Ipilimumab
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved the GVAX vaccine as a treatment for any disease. The U.S. Food and Drug Administration (FDA) has not approved nivolumab or ipilimumab for your specific disease but it has been approved for other uses. The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits. This phase 1 study will be conducted in 2 parts * In the first part, participants will, as part of standard of care procedure to remove cancerous tissue, undergo neuroblastoma cell collection from a portion of resected tumor. * Those cells will then be used to create the vaccine which will be stored for potential use during the second part of this research study. * In the second part, participants who did not respond to standard therapy will receive the GVAX vaccine along with nivolumab and ipilimumab. The study treatment will continue for up to 24 months and participants will be followed for 2 years after last study treatment (if received at least one vaccination).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Collection of cancerous tissue to create GVAX vaccine or irradiated GMCSF-secreting autologous neuroblastoma cell vaccine at time of clinically indicated surgical procedure
Vaccine injected weekly over initial 21 day cycle, biweekly for cycles 2-4 of 21 day cycle duration and cycles 5 and subsequent of 28 day cycle duration until vaccine supply is exhausted.
Intravenous infusion of nivolumab every 3 weeks, for cycles 1-4. Cycles 1-4 are 21 days Intravenous infusion of nivolumab biweekly for cycle 5 and subsequent of 28 day cycle duration. Subsequent 28 day cycles will last up to 2 years.
Boston Children's Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institite
Boston, Massachusetts, United States
The number of participants with grade 4 toxicities
To assess safety, the number of grade 4 toxicities associated with vaccine and nivolumab/ipilimumab using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5
Time frame: Up to 2 years
Number of Participants to receive 6 vaccinations
Feasibility will be assessed by the ability to make vaccine from available biopsy material in quantities sufficient for six vaccinations, for a given patient. A success rate (number of patients for whom quantity sufficient for six vaccinations exist / total number of eligible patients) under 65% may imply that the method needs further development or that the amount of tissue available in this population limits the feasibility of this strategy. Total number of vaccine doses administered per patient will also be counted
Time frame: Up to 2 years
Progression-free survival (PFS)
Kaplan-Meier plots, 1-year PFS estimate will be calculated, along with the standard errors
Time frame: time from receipt of first GVAX vaccine dose to the earlier of progression, relapse or death due to disease up to 48 months
Overall best response
Each patient will be categorized as a responder (≥PR) or a non-responder (\<PR) by INRC criteria
Time frame: Start of the treatment until disease progression/recurrence up to 48 months
Overall Survival
Kaplan-Meier plots, 1-year OS estimates will be calculated, along with the standard errors
Time frame: Time from receipt of the first GVAX vaccine dose to death due to any cause up to 48 months
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Intravenous infusion of ipilimumab every 3 weeks, for cycles 1-4. Cycles 1-4 are 21 days