Clinical trial NCT03334305: 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).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Malignant Glioma
High Grade Glioma
Keywords: Immunotherapy
Pediatric
Vaccine Therapy
Young adult
Immune system
Dendritic Cell
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Pediatric Cancer Foundation
name: National Cancer Institute (NCI)
name: Moffitt Clinical Research Network (MCRN)
name: National Institutes of Health (NIH)
First posted: 2017-11-07
Enrollment: 18
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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
* 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 leukapheresis.

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.

Primary outcomes:
measure: Evaluate safety of TTRNA-DCs and TTRNA-xALT
timeFrame: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death
Secondary outcomes:
measure: Determine feasibility of completing treatment
timeFrame: Up to 10 months
measure: Anti-tumor immune responses
timeFrame: up to 10 months
measure: Progression-free survival (PFS)
timeFrame: Up to 8 years
measure: Overall survival (OS)
timeFrame: Up to 8 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama at UAB
state: Alabama
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: UF Health Shands Children's Hospital
state: Florida
Study officials:
affiliation: University of Florida
name: Elias Sayour, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Duane Mitchell, MD, PhD
role: STUDY_CHAIR
References: