ACTION Trial: Adoptive Cellular Therapy Following Dose-Intensified Temozolomide in Newly-diagnosed Pediatric High-grade Gliomas (Phase I).

IRB201701867-N

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.

2018-05-16

2026-05-01

2028-05-01

Active (not recruiting)

Early phase I

10

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ESTIMATED'}}

2024-04-17