Clinical Trials /

GVAX Plus Checkpoint Blockade in Neuroblastoma

NCT04239040

Description:

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

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: GVAX Plus Checkpoint Blockade in Neuroblastoma
  • Official Title: A Phase 1 Study of Combination Nivolumab and Ipilimumab With Irradiated GM-CSF Secreting Autologous Neuroblastoma Cell Vaccine (GVAX) for Relapsed or Refractory Neuroblastoma

Clinical Trial IDs

  • ORG STUDY ID: 19-680
  • NCT ID: NCT04239040

Conditions

  • Neuroblastoma
  • Pediatric Solid Tumor

Interventions

DrugSynonymsArms
GVAX vaccineGMCSF-secreting autologous neuroblastoma cell vaccineHigh Risk Neuroblastoma
NivolumabOpdivoHigh Risk Neuroblastoma
IpilimumabYervoyHigh Risk Neuroblastoma

Purpose

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

Detailed Description

      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).
    

Trial Arms

NameTypeDescriptionInterventions
High Risk NeuroblastomaExperimentalTissue Collection of Cancerous cells during primary 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.
  • GVAX vaccine
  • Nivolumab
  • Ipilimumab
Relapsed or Refractory High Risk NeuroblastomaExperimentalTissue Collection of Cancerous cells during 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.
  • GVAX vaccine
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  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

               -  Age > 1 year of age

               -  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

                    -  131I- MIBG therapy ≥ 6 weeks

                    -  Autologous stem cell infusion following myeloablative therapy ≥ 6 weeks

                    -  Any other investigational agents ≥ 14 days

          -  Organ function requirements

               -  Adequate bone marrow function defined as:

                    -  ANC >/= 500/µL

                    -  Hgb >8 (may not be transfused)

                    -  Platelet count ≥30,000 (may not be transfused)

               -  Hepatic Function:

                    -  Total bilirubin ≤ 1.5 x upper limit of normal for age

                    -  ALT (SGPT) ≤ 3 x upper limit of normal (135 U/L) For the purpose of this
                       study, the ULN for ALT is 45 U/L

               -  Renal Function, a serum creatinine based on age/sex as follows:

                    -  Maximum Serum Creatinine (mg/dL)

                         -  Age 1 to <2 years Male: 0.6 Female: 0.6

                         -  Age 2 to < 6 years Male:0.8 Female 0.8

                         -  Age 6 to < 10 years Male:1 Female: 1

                         -  Age 10 to < 13 years Male: 1.2 Female: 1.2

                         -  Age 13 to < 16 years Male: 1.5 Female: 1.4

                         -  Age ≥ 16 years Male: 1.7 Female: 1.4

                    -  OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine
                       levels greater than the above age/sex maximum allowed values

               -  Adequate Pulmonary Function Defined as:

                    -  No evidence of dyspnea at rest

                    -  No exercise intolerance due to pulmonary insufficiency

                    -  Pulse oximetry > 92% while breathing room air

               -  Adequate pancreatic function defined as

                    -  Serum lipase </= ULN at baseline.

               -  No ≥ Grade 2 non-hematologic toxicity

               -  Absolute eosinophil count ≤ 5000/ul

               -  Negative B-HCG pregnancy test in females of childbearing potential. Must be drawn
                  or repeated within 24 hours prior to initial administration of study drugs

               -  Women of childbearing potential (WOCBP) receiving nivolumab will be agree to
                  adhere to contraception for a period of 5 months after the last dose of
                  nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will
                  agree to adhere to contraception for a period of 7 months after the last dose of
                  nivolumab.

        Exclusion Criteria:

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of participants with grade 4 toxicities
Time Frame:Up to 2 years
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
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
Safety Issue:
Description:Kaplan-Meier plots, 1-year PFS estimate will be calculated, along with the standard errors
Measure:Overall best response
Time Frame:Start of the treatment until disease progression/recurrence up to 48 months
Safety Issue:
Description:Each patient will be categorized as a responder (≥PR) or a non-responder (<PR) by INRC criteria
Measure:Overall Survival
Time Frame:Time from receipt of the first GVAX vaccine dose to death due to any cause up to 48 months
Safety Issue:
Description:Kaplan-Meier plots, 1-year OS estimates will be calculated, along with the standard errors

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

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

Last Updated

January 21, 2020