Brain Stem Gliomas Treated With Adoptive Cellular Therapy During Focal Radiotherapy Recovery Alone or With Dose-intensified Temozolomide (Phase I)

Summary

The standard of care for children with DIPG includes focal radiotherapy (RT) but outcomes have remained dismal despite this treatment. The addition of oral Temozolomide (TMZ) concurrently with RT followed by monthly TMZ was also found to be safe but ineffective. Recent studies in adults have shown that certain types of chemotherapy induce a profound but transient lymphopenia (low blood lymphocytes) and vaccinating and/or the adoptive transfer of tumor-specific lymphocytes into the cancer patient during this lymphopenic state leads to dramatic T cell expansion and potent immunologic and clinical responses. Therefore, patients in this study will either receive concurrent TMZ during RT and immunotherapy during and after maintenance cycles of dose-intensive TMZ (Group A) or focal radiotherapy alone and immunotherapy without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups.

Conditions

• Diffuse Intrinsic Pontine Glioma (DIPG)
• Brain Stem 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.

BIOLOGICAL

TTRNA-xALT

During TMZ Cycle 4 and with DC vaccine #6, an infusion of T-cells will be administered to all subjects.

DRUG

Cyclophosphamide + Fludarabine Lymphodepletive Conditioning

Subjects in Group B, however, will receive lymphodepletion with cyclophosphamide + fludarabine after DC vaccination and prior to the intravenous infusion of ex vivo expanded tumor-reactive lymphocytes.

DRUG

Dose-Intensified TMZ

After chemoradiation, subjects in Group A 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.

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.

BIOLOGICAL

Autologous Hematopoietic Stem Cells (HSC)

During Cycle 4, all patients will receive HSCs prior to xALT infusion and DC vaccine #6.

Sponsors & Collaborators

• Accelerate Brain Cancer Cure

  collaborator OTHER

• Lyla Nsouli Foundation

  collaborator UNKNOWN

• University of Florida

  lead OTHER

Principal Investigators

• Elias Sayour, MD, PhD · University of Florida

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

3 Years

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-07-17

Primary Completion

2025-03-20

Completion

2025-03-20

FDA Drug

Yes

Countries

• United States

Study Locations