This phase I trial studies the best dose and side effects of GD2 specific chimeric antigen receptor (CAR) and interleukin-15 (IL-15) expressing autologous natural killer T-cells (G28z.15 NKTs) with or without etanercept in treating children with neuroblastoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). This trial combines two different ways of fighting cancer: antibodies and natural killer T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. GD2-CAR natural killer T cells are modified immune cells that have been engineered in the laboratory to specifically target GD2 proteins found on neuroblastoma tumor cells and kill them. IL-15 is critical for the development and maintenance of T cells. These new cells may be able to slow the growth of tumor cells. Etanercept can slow down neuroblastoma growth, which might enhance the effects of the modified immune cells. Giving GD2-CAR natural killer T cells with or without etanercept may be safe, tolerable, and/or effective in treating patients with relapsed or refractory neuroblastoma.
Additional locations may be listed on ClinicalTrials.gov for NCT03294954.
Locations matching your search criteria
United States
Texas
Houston
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterStatus: Active
Contact: Gengwen Tian
Phone: 832-824-4233
Texas Children's HospitalStatus: Active
Contact: Gengwen Tian
Phone: 832-824-4233
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and safety profile of autologous natural-killer T cells (NKTs) expressing a 2nd generation GD2-specific chimeric antigen receptor that incorporates the co-stimulatory endodomain of CD28 in addition to the CD3 zeta chain as well as interleukin-15 (hereafter referred to as autologous anti-GD2CAR-CD28-CD3zeta-IL-15-expressing natural killer T-cells [G28z.15 NKTs]) alone or in combination with etanercept administered to patients with relapsed or refractory neuroblastoma.
Ia. Assess the MTD of G28z.15 NKTs adoptively transferred to patients with relapsed or refractory neuroblastoma in combination with etanercept;
Ib. Assess the safety profile of G28z.15 NKTs adoptively transferred to patients with relapsed/refractory neuroblastoma in combination with etanercept.
SECONDARY OBJECTIVES:
I. To evaluate the anti-tumor response of autologous G28z.15 NKT cells in patients with relapsed/refractory neuroblastoma and compare the anti-tumor response in patients treated with and without etanercept.
Ia. Evaluate residual disease sites for changes in tumor mass dimensions using 3-dimensional (3D) imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) after the administration of autologous G28z.15 NKT cells;
Ib. Determine the number of detectable metaiodobenzylguanidine (MIBG) avid disease or bone scan positive sites in response to the administration of autologous G28z.15 NKT cells;
Ic. Assess bone marrow clearance among children with bone marrow involvement at the time of enrollment after the administration of autologous G28z.15 NKT cells.
EXPLORATORY OBJECTIVES:
I. To evaluate the immunologic response of autologous G28z.15 NKT cells with and without Etanercept in patients with relapsed/refractory neuroblastoma.
Ia. Assess the expansion and functional persistence of G28z.15 NKTs in the peripheral blood of patients using transgene detection by quantitative real-time polymerase chain reaction (PCR) and flow cytometry;
Ib. Assess the frequency of NKT target cells: CD1d+CD33+CD14+CD163+/-myelomonocytic cells in blood and in tumor biopsies and bone marrow (BM) aspirates (when available);
Ic. Assess the frequency and activation status (CD69) of natural killer (NK) cells (CD3-CD56+);
Id. Assess the sequential changes in patients’ serum cytokine and chemokine levels after G28z.15 NKT infusion with and without etanercept;
Ie. Assess the changes in CAR NKTs and cancer cells post-infusion in tumor biopsies.
OUTLINE: This is a dose-escalation study of G28z.15 NKTs alone and in combination with etanercept.
Patients undergo leukapheresis at least 1 month prior to anticipated NKT cell infusion date. Patients then receive cyclophosphamide intravenously (IV) on days -4 and -3, fludarabine IV on days -4 to -2, and G28z.15 NKTs IV over 10 minutes on day 0. Patients may also receive etanercept subcutaneously (SC) on days -1, +6, +13, +20, and +27 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT, MRI, bone scan, MIBG imaging, and/or positron emission tomography (PET) throughout the study. Patients may also undergo bone marrow aspiration and biopsy if clinically indicated throughout the study.
After completion of study treatment, patients are followed up at 1, 2, 3, 4, and 8 weeks, 3, 6, 9, and 12 months, every 6 months for 4 years, and annually thereafter for 10 years.
Lead OrganizationBaylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Principal InvestigatorGengwen Tian