Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas

NCT03334305 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB201701867-NR01CA195563OCR15852
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

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.

Conditions

High Grade Glioma; Malignant Glioma

Keywords

Immunotherapy; Pediatric; Vaccine Therapy; Young adult; Immune system; Dendritic Cell

Outcome Measures

Primary Outcomes (1)

• Evaluate Safety of TTRNA-DCs and TTRNA-xALT

  Percentage of subjects with grade 3 or greater adverse events. Adverse events (AEs) were summarized in the safety population (N = 5) at the participant level. For each AE term, a participant was counted once using the maximum observed CTCAE grade. Recurrent occurrences of the same AE in a participant were not counted multiple times.

  From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death, whichever occurs first, up to 10 months

Secondary Outcomes (4)

• Determine Feasibility of Completing Treatment

  Up to 10 months

• Change in CD4:CD8 T-cell Ratio

  baseline to up to 10 months after initiation of treatment

• Progression-free Survival (PFS)

  From date of first treatment until documented disease progression or death, assessed during study follow-up (up to approximately 3 years)

• Overall Survival (OS)

  From date of first treatment until death from any cause, assessed during study follow-up (up to approximately 3 years)

Study Arms (2)

Group A

EXPERIMENTAL

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

Biological: TTRNA-DC vaccines with GM-CSF; Drug: Dose-intensified TMZ; Biological: TTRNA-xALT; Drug: Td vaccine

Group B

EXPERIMENTAL

Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)

Biological: TTRNA-DC vaccines with GM-CSF; Drug: Dose-intensified TMZ; Biological: Autologous Hematopoietic Stem cells (HSCs); Biological: TTRNA-xALT; Drug: Td vaccine

Interventions

TTRNA-DC vaccines with GM-CSF BIOLOGICAL

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.

Group A; Group B

Dose-intensified TMZ DRUG

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.

Group A; Group B

TTRNA-xALT BIOLOGICAL

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

Group A; Group B

Td vaccine DRUG

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.

Group A; Group B

Autologous Hematopoietic Stem cells (HSCs) BIOLOGICAL

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.

Group B

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institutes of Health (NIH): collaborator
• University of Florida: lead
• National Pediatric Cancer Foundation: collaborator
• National Cancer Institute (NCI): collaborator
• Moffitt Clinical Research Network (MCRN): collaborator

Study Sites (3)

Children's of Alabama at UAB

Birmingham, Alabama, 35233, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

UF Health Shands Children's Hospital

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Diphtheria-Tetanus Vaccine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined

Results Point of Contact

• Title: Duane Mitchell, MD, PhD
• Organization: University of Florida

duane.mitchell@neurosurgery.ufl.edu

352-273-9000

Study Officials

• Elias Sayour, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Duane Mitchell, MD, PhD

  University of Florida

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2017
• First Posted: November 7, 2017
• Study Start: August 27, 2018
• Primary Completion: March 20, 2025
• Study Completion: March 20, 2025
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)