Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas
Purpose
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
Eligibility
- Eligible Ages
- Between 3 Years and 21 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Group A |
Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) |
|
|
Experimental Group B |
Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) |
|
Recruiting Locations
More Details
- NCT ID
- NCT03334305
- Status
- Active, not recruiting
- Sponsor
- University of Florida
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.