Clinical Trials /

Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas

NCT03334305

Description:

It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. In most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use a patient's tumor to make a vaccine which we hope will stimulate T-cells to kill tumor cells and leave normal cells alone. High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation. The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate a person's immune system to fight off the tumor cells in the brain.

Related Conditions:
  • Malignant Glioma
  • WHO Grade III Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas
  • Official Title: ACTION Trial: Adoptive Cellular Therapy Following Dose-Intensified Temozolomide in Newly-diagnosed Pediatric High-grade Gliomas (Phase I).

Clinical Trial IDs

  • ORG STUDY ID: IRB201701867-N
  • SECONDARY ID: R01CA195563
  • SECONDARY ID: OCR15852
  • NCT ID: NCT03334305

Conditions

  • Malignant Glioma

Interventions

DrugSynonymsArms
TTRNA-DC vaccines with GM-CSFGroup A
Dose-intensified TMZGroup A
Autologous Hematopoietic Stem cells (HSCs)Group B
TTRNA-xALTGroup A
Td vaccineGroup A

Purpose

It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. In most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use a patient's tumor to make a vaccine which we hope will stimulate T-cells to kill tumor cells and leave normal cells alone. High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation. The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate a person's immune system to fight off the tumor cells in the brain.

Detailed Description

      It is believed that the body's immune system protects the body by attacking and killing tumor
      cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they
      recognize special proteins on the surface of tumors. But in most patients with advanced
      cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will
      use your tumor to make a vaccine which we hope will stimulate your T-cells to kill tumor
      cells and leave your normal cells alone.

      High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to
      attack. Before T-cells can become active against tumor cells, they require strong stimulation
      by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of
      the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes,
      and create this strong stimulation.

      The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC
      vaccines can be given safely. Most importantly, this study is also to determine whether the
      T-cells and DC vaccines can stimulate your immune system to fight off the tumor cells in your
      brain. When the vaccine for this study is made, dendritic cells will be loaded with genetic
      material called RNA (ribonucleic acid) from your tumor to stimulate the dendritic cells. The
      vaccine has two components given at different times after chemoradiation and throughout
      chemotherapy cycles. The first part, the DC vaccine, involves RNA loaded dendritic cells that
      are given under the skin at several time points in the study and the second part, xALT
      vaccine, is a single infusion of tumor-specific T cells delivered through one of two
      peripheral IV catheters that are placed prior to infusion. This vaccine is investigational
      which means that it is not approved by the US Food and Drug Administration (FDA) and is being
      tested in research studies.

      It is hoped that by injecting the DC vaccine into your skin and infusing the T-cells into
      your blood, your immune system will be activated against the tumor. Once it is activated
      against the tumor, your immune system may recognize and attack the tumor cells in your brain
      and not attack normal cells. Use of a vaccine that stimulates your immune system is called
      immunotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Group AExperimentalDose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs)
  • TTRNA-DC vaccines with GM-CSF
  • Dose-intensified TMZ
  • TTRNA-xALT
  • Td vaccine
Group BExperimentalDose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)
  • TTRNA-DC vaccines with GM-CSF
  • Dose-intensified TMZ
  • Autologous Hematopoietic Stem cells (HSCs)
  • TTRNA-xALT
  • Td vaccine

Eligibility Criteria

        Screening Eligibility:

          -  Patients with histologically confirmed WHO Grade III or IV malignant glioma

          -  Scheduled for definitive surgical resection of suspected HGG (biopsy only subjects are
             not eligible for this study)

        Post-Surgical Resection Eligibility

          -  Histologically confirmed WHO Grade III or IV malignant glioma

          -  Residual post-surgical disease burden < 3 cm as defined by longest perpendicular
             diameter of contrast enhancing tumor on post-operative MRI Karnofsky Performance
             Status (KPS) of > 60% (KPS for > 16 years of age) or Lansky performance Score (LPS) of
             ≥ 60 (LPS for ≤ 16 years of age) assessed within 2 weeks prior to registration

          -  Bone Marrow: ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported); Platelets ≥
             100,000/µl (unsupported for at least 3 days); Hemoglobin > 8 g/dL (may be supported)

          -  Renal:Serum creatinine ≤ upper limit of institutional normal Hepatic: Bilirubin ≤ 1.5
             times upper limit of institutional normal for age. SGPT (ALT) ≤ 3 times upper limit of
             institutional normal for age. SGOT (AST) ≤ 3 times upper limit of institutional normal
             for age.

          -  Signed informed consent according to institutional guidelines.

          -  Patient or patient guardian consent to PBSC harvest following registration.

          -  Subjects of childbearing or child-fathering potential must be willing to use medically
             acceptable forms of birth control while being treated on this study.

          -  Subjects with post-surgical neurological deficits should have deficits that are stable
             for a minimum of 1 week prior to registration.

        Prior to 1st Vaccine

        - Off corticosteroids or weaning to a minimal/stable dose of replacement steroids ≤ 4
        mg/day within 1 week of scheduled DC vaccination.

        Exclusion Criteria:

          -  HGG biopsy only subjects are not eligible for this study

          -  Midline unresectable tumors

          -  Gliomatosis Cerebri

          -  Residual post-surgical disease burden > 3 cm as defined by longest perpendicular
             diameter of contrast enhancing tumor on MRI.

          -  Pregnant or need to breast feed during the study period (Negative serum pregnancy test
             required).

          -  Known autoimmune or immunosuppressive disease or human immunodeficiency virus
             infection.

          -  Subjects with significant renal, cardiac (congestive cardiac failure, myocardial
             infarction, myocarditis), pulmonary, hepatic or other organ dysfunction.

          -  Subjects who require corticosteroids above physiologic doses (>4mg/day or equivalent
             dexamethasone).

          -  Severe or unstable concurrent medical conditions.

          -  Prior allergic reaction to TMZ, GM-CSF, or Td

          -  Subjects who are unwilling or unable to receive treatment and undergo follow-up
             evaluations at the enrolled Sunshine Project Consortium treatment site.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate safety of TTRNA-DCs and TTRNA-xALT
Time Frame:From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death
Safety Issue:
Description:Number of subjects with immunotherapy-related dose-limiting toxicities including 1) Grade III or greater non-neurologic toxicity; 2) Grade III neurologic toxicity that does not improve to Grade II or better within 5 days; or 3) Grade IV neurologic toxicity.

Secondary Outcome Measures

Measure:Determine feasibility of completing treatment
Time Frame:Up to 10 months
Safety Issue:
Description:Number of subjects completing treatment
Measure:Anti-tumor immune responses
Time Frame:up to 10 months
Safety Issue:
Description:Estimate the mean difference and the variation in INF gamma secretion
Measure:Progression-free survival (PFS)
Time Frame:Up to 8 years
Safety Issue:
Description:Days of PFS
Measure:Overall survival (OS)
Time Frame:Up to 8 years
Safety Issue:
Description:Days of OS

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Florida

Last Updated

December 17, 2019