Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas

Phase 1

Active, not recruiting

• Conditions: High Grade Glioma; Malignant Glioma
• Interventions: Biological: TTRNA-DC vaccines with GM-CSF; Drug: Dose-intensified TMZ; Biological: TTRNA-xALT; Biological: Autologous Hematopoietic Stem cells (HSCs); Drug: Td vaccine

• Registration Number: NCT03334305
• Lead Sponsor: University of Florida

Brief Summary

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.

Study Timeline

• Study First Submitted: 2017-10-26
• Study First Submitted QC: 2017-11-02
• Study First Posted: 2017-11-07
• Study Start: 2018-05-16
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-19
• Primary Completion: 2026-05
• Study Completion: 2028-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

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Exclusion Criteria

• 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.
• 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group A	Dose-intensified TMZ	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs)
Group A	TTRNA-xALT	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs)
Group A	Td vaccine	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs)
Group B	TTRNA-DC vaccines with GM-CSF	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)
Group B	Autologous Hematopoietic Stem cells (HSCs)	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)
Group B	TTRNA-xALT	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)
Group A	TTRNA-DC vaccines with GM-CSF	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs)
Group B	Dose-intensified TMZ	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)
Group B	Td vaccine	Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)

Primary Outcome Measures

Name	Time	Method
Evaluate safety of TTRNA-DCs and TTRNA-xALT	From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death	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

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

Trial Locations

Locations (3)

Children's of Alabama at UAB; 🇺🇸 Birmingham, Alabama, United States

Children's National Hospital; 🇺🇸 Washington, District of Columbia, United States

UF Health Shands Children's Hospital; 🇺🇸 Gainesville, Florida, United States