GVAX Plus Checkpoint Blockade in Neuroblastoma

NCT04239040 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 19-680
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Neuroblastoma; Pediatric Solid Tumor

Keywords

Neuroblastoma; Pediatric Solid Tumor; Immunotherapy; GVAX Vaccine; Nivolumab; Ipilimumab

Outcome Measures

Primary Outcomes (2)

• 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

  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

  Up to 2 years

Secondary Outcomes (3)

• Progression-free survival (PFS)

  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

  Start of the treatment until disease progression/recurrence up to 48 months

• Overall Survival

  Time from receipt of the first GVAX vaccine dose to death due to any cause up to 48 months

Study Arms (1)

Relapsed or Refractory High Risk Neuroblastoma

EXPERIMENTAL

Tissue Collection of Cancerous cells during primary or clinically indicated surgical resection. Manufacture and cryopreservation of vaccine. Treatment with vaccine, nivolumab and ipilimumab. * 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 ipilimumab 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.

Procedure: Tissue collection; Biological: GVAX vaccine; Drug: Nivolumab; Drug: Ipilimumab

Interventions

Tissue collection PROCEDURE

Collection of cancerous tissue to create GVAX vaccine or irradiated GMCSF-secreting autologous neuroblastoma cell vaccine at time of clinically indicated surgical procedure

Relapsed or Refractory High Risk Neuroblastoma

GVAX vaccine BIOLOGICAL

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.

Also known as: GMCSF-secreting autologous neuroblastoma cell vaccine

Relapsed or Refractory High Risk Neuroblastoma

Nivolumab DRUG

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.

Also known as: Opdivo

Relapsed or Refractory High Risk Neuroblastoma

Ipilimumab DRUG

Intravenous infusion of ipilimumab every 3 weeks, for cycles 1-4. Cycles 1-4 are 21 days

Also known as: Yervoy

Relapsed or Refractory High Risk Neuroblastoma

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility Criteria for neuroblastoma cell collection and vaccine manufacture
• Patients with histologically confirmed neuroblastoma, who meet the Children's Oncology Group (COG) high-risk group assignment criteria
• Lansky/Karnofsky performance status ≥50% (see Appendix A)
• Participants must have clinical indication for surgical resection of their neuroblastoma and undergo resection at Boston Children's Hospital
• Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document.
• Eligibility Criteria to commence to receive study treatment with irradiated GM-CSF secreting autologous tumor vaccine, nivolumab, and ipilimumab
• Histologically confirmed high-risk neuroblastoma based on COG assignment criteria
• Residual disease at the end of standard therapy or relapsed neuroblastoma in any disease state (including CR) by clinical criteria (histologic confirmation of relapse or residual disease is not required).
• Age \> 1 year of age
• Lansky/Karnofsky performance status ≥50% (see Appendix A)
• Prior Therapy - Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimal duration from prior anti-cancer directed therapy prior to enrollment
• Myelosuppressive Chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy
• Small molecule biologic therapy: At least 7 days following the last dose of a biologic agent.
• Monoclonal antibodies ≥ 7 days or 3 half-lives whichever is longer but no longer than 30 days (with recovery of any associated toxicities)
• External beam irradiation: ≥ 14 days after small port XRT, ≥ 12 weeks after large port radiation (≥ 50% of the marrow space) including total body irradiation, craniospinal radiation, whole abdomen and whole lung radiation

You may not qualify if:

• Participants who are receiving any other investigational agents.
• No systemic corticosteroid therapy, other than replacement therapy for adrenal insufficiency or transfusion premedication. Participants who are receiving or have received lympholytic steroid (\>=40mg/m2 prednisone equivalent) therapy within 4 weeks of first anticipated vaccine administration are excluded, because high-dose steroid therapy is expected to significantly limit the ability of the immune system to respond to GVAX vaccination.
• Participants with known parenchymal brain metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GM-CSF or DMSO.
• Participants with any form of primary immunodeficiency.
• Females who are pregnant are excluded from this study because GVAX is an investigational biologic with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GVAX, breastfeeding should be discontinued if the mother is treated with GVAX
• Uncontrolled intercurrent illness or serious uncontrolled medical disorder including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and/or pronounced disturbances of the electrical conduction system of the heart or psychiatric illness/social situations that would limit compliance with study requirements.
• Known HIV-positive participants on combination antiretroviral therapy are ineligible because of the effect of GVAX vaccination on the disease course is unknown and because the underlying disease is expected to limit the ability of the immune system to respond to GVAX vaccination.
• Clinically relevant known active infection including active hepatitis B or C or any other concurrent disease which in the judgment of the Investigator would make the subject inappropriate for enrollment on this study
• History of a malignancy other than neuroblastoma with exception of the following circumstances:
• Patients with a history of malignancy who have been adequately treated and have been disease-free for at least 2 years are not excluded.
• Patients with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers) are not excluded.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti PD L2 or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX 40, CD137).
• Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are exceptions. Intermittent use of bronchodilators or local steroid injections are not excluded. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diagnoses not listed must be approved by the protocol chair.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institite

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Tissue Banks; GVAX vaccine; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Biological Specimen Banks; Health Facilities; Health Care Facilities Workforce and Services; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Natalie B Collins, MD, PHD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: January 23, 2020
• Study Start: January 29, 2020
• Primary Completion: January 27, 2024
• Study Completion: February 29, 2024
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)