This phase I trial investigates the side effects and best dose of autologous GD2 chimeric antigen receptor (CAR) T cells (GD2CART) and how well it works in treating patients with diffuse intrinsic pontine glioma or spinal diffuse midline glioma. The chimeric antigen receptor (CAR) is a genetically-engineered receptor made so that immune cells can recognize and respond to a specific molecule, which in this trial is the GD2 protein. This uses a portion of an antibody to GD2 and part of a molecule that activates or ‘turns on’ the immune cell. The CAR molecule is combined with a patient's T cells, to help the T cells find cancer in the body. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, are given before GD2CART to help prepare the immune system to accept GD2CART, and may help let the GD2CART grow in the body and attack cancer cells. The purpose of this trial is to test the safety of giving GD2CART to children and young adults with diffuse intrinsic pontine glioma or diffuse midline glioma, and determine its effects, both good and bad, and to test how the cancer responds to GD2CART after chemotherapy.
Additional locations may be listed on ClinicalTrials.gov for NCT04196413.
Locations matching your search criteria
United States
California
Palo Alto
Lucile Packard Children's Hospital Stanford UniversityStatus: Active
Contact: Michelle Monje
Phone: 650-721-5750
Stanford Cancer Institute Palo AltoStatus: Active
Contact: Michelle Monje
Phone: 650-721-5750
PRIMARY OBJECTIVES:
I. Determine the feasibility of manufacturing autologous T cells transduced with 14g2a-CD8-BBz-iCasp9 retroviral vector expressing GD2 chimeric antigen receptor (autologous anti-GD2-CAR-BBz-iCasp9 retroviral vector-transduced T lymphocytes [GD2CART]) for administration in subjects with H3K27M+ diffuse intrinsic pontine glioma (DIPG) or subjects with spinal H3 K27M-mutant diffuse midline glioma (DMG) using a retroviral vector and dasatinib in the Miltenyi CliniMACS Prodigy system.
II. Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of GD2CART in subjects with H3K27M+ DIPG administered after cyclophosphamide/fludarabine-based lymphodepletion regimen using the following dose escalation schedule: dose level (DL) 1: 1e6 transduced T cells/kg; DL2: 3e6 transduced T cells/kg; DL3: 10e6 transduced T cells/kg.
III. Assess the safety of the MTD/RP2D of GD2CART in subjects with spinal H3K27M mutant DMG.
SECONDARY OBJECTIVES:
I. In a preliminary manner, assess clinical benefit of GD2CART at the RP2D in subjects with H3K27M DIPG or spinal H3 K27M-mutant DMG.
II. If unacceptable toxicity occurs that is possibly, probably or likely related to GD2CART, assess the capacity for rimiducid (AP1903), a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.
EXPLORATORY OBJECTIVES:
I. Measure expansion/persistence/phenotype of adoptively transferred GD2CART in the cerebrospinal (CSF) and blood and correlate this with antitumor effects.
II. Conduct analyses of the manufactured T cell product and blood and CSF post-infusion to identify biomarkers associated with enhanced CAR T cell expansion, persistence and/or phenotype.
III. Assess whether changes in the level of circulating tumor deoxyribonucleic acid (ctDNA) in the cerebrospinal fluid can provide prognostic information and/or information regarding clonal evolution of DIPG over time.
IV. Evaluate whether antigen expression or tumor microenvironment are correlated with response to CAR T cell.
OUTLINE: This is a dose-escalation study of autologous anti-GD2-CAR-BBz-iCasp9 retroviral vector-transduced T lymphocytes.
CONDITIONING LYMPHODEPLETION CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine phosphate IV over 30 minutes on daily on days -4 to -2.
GD2CART INFUSION: Patients receive autologous anti-GD2-CAR-BBz-iCasp9 retroviral vector-transduced T lymphocytes (GD2CART) IV over 10-30 minutes on day 0. Beginning on day 30, patients who had a partial response or stable disease with clinical benefit may receive another infusion of cells.
After completion of study treatment, patients are followed up for 28 days, at 2 months, 3 months, 6 months, 9 months, 12 months, every 6-12 months until year 5, and then annually for years 6-15.
Lead OrganizationLucile Packard Children's Hospital Stanford University
Principal InvestigatorMichelle Monje