Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas

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.

Conditions

• Malignant Glioma
• High Grade Glioma

Interventions

BIOLOGICAL

TTRNA-DC vaccines with GM-CSF

After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal.

DRUG

Dose-intensified TMZ

After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations.

BIOLOGICAL

Autologous Hematopoietic Stem cells (HSCs)

Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion.

BIOLOGICAL

TTRNA-xALT

During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects.

DRUG

Td vaccine

A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.

Sponsors & Collaborators

• National Pediatric Cancer Foundation

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• Moffitt Clinical Research Network (MCRN)

  collaborator UNKNOWN

• National Institutes of Health (NIH)

  collaborator NIH

• University of Florida

  lead OTHER

Principal Investigators

• Elias Sayour, MD, PhD · University of Florida

• Duane Mitchell, MD, PhD · University of Florida

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

3 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-08-27

Primary Completion

2025-03-20

Completion

2025-03-20

FDA Drug

Yes

Countries

• United States

Study Locations