Testing a New Immune Cell Therapy, GD2-Targeted Modified T-cells (GD2CART), in Children, Adolescents, and Young Adults With Relapsed/Refractory Osteosarcoma and Neuroblastoma, GD2-CAR PERSIST Trial

Paused · Phase 1

Conditions studied: Recurrent Childhood Neuroblastoma, Recurrent Childhood Osteosarcoma, Recurrent Neuroblastoma, Recurrent Osteosarcoma, Refractory Childhood Neuroblastoma, Refractory Childhood Osteosarcoma, Refractory Neuroblastoma, Refractory Osteosarcoma

In brief

This phase I trial investigates the side effects and determines the best dose of an immune cell therapy called GD2CART, as well as how well it works in treating patients with osteosarcoma or neuroblastoma that has come back (relapsed) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this trial will come from the patient and will have a new gene put in them that makes them able to recognize GD2, a protein on the surface of tumor cells. These GD2-specific T cells may help the body's immune system identify and kill GD2 positive tumor cells.

Key facts

Study ID

NCT04539366

Run by

National Cancer Institute (NCI)

People needed

73

Starts

2022-01-25

Expected to finish

2040-12-31

Last updated by the study team

2026-08-05

Who can join

Age: any, up to 40. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Must have histologically confirmed neuroblastoma or osteosarcoma that is recurrent or refractory and for which standard curative measures do not exist or are no longer effective. Must have histologic verification of their disease at diagnosis or at relapse
• Patients with osteosarcoma in the dose escalation cohort, must have evaluable or measurable disease at enrollment
• Patients with osteosarcoma in the expansion cohort must have measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at enrollment
• Patients with neuroblastoma in the dose escalation or dose the expansion cohort must have:
• Prior progressive disease OR refractory disease present since diagnosis AND at least one of the following:
• Evidence of tumor in the bone marrow (BM) less than or equal to 5%
• At least one metaiodobenzylguanidine (MIBG)-avid soft tissue or skeletal site
• For MIBG-nonavid disease, at least one FDG-PET- positive soft tissue or skeletal site plus past histologic confirmation
• Progressive disease is defined as any disease progression occurring at any time after the diagnosis of high-risk neuroblastoma. Refractory disease is defined as an incomplete response of high-risk neuroblastoma to all treatments but without disease progression
• NOTE: Disease assessment will be required within 2 weeks prior to lymphodepleting chemotherapy. Patients will need to meet criteria for having low burden disease prior to the start of lymphodepleting chemotherapy
• Must be < 40 years of age
• There is no limit to the number of prior treatment regimens. The following washout periods prior to leukapheresis apply to patients undergoing leukapheresis on this study. If a patient has cryopreserved peripheral blood mononuclear cells (PBMCs) stored, the following washout periods are strongly recommended but not required and the product is useable if it meets the criteria established in this Investigational New Drug (IND)
• Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of leukapheresis (6 weeks if prior nitrosourea)
• Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a short-acting growth factor. At least 14 days must have elapsed after receiving pegfilgrastim
• Biological agent, tyrosine kinase inhibitor, targeted agent, metronomic chemotherapy: At least 7 days must have elapsed since the completion of therapy with a biologic agent, tyrosine kinase inhibitor, targeted agent, or metronomic non-myelosuppressive regimen
• 131I-MIBG or other radioisotope therapy: At least 6 weeks must have elapsed since prior therapy with 131I-MIBG. At least 6 weeks or 10 half-lives (whichever is shorter) must have elapsed since prior therapy with any other radioisotope
• Monoclonal antibodies and checkpoint inhibitors: At least 3 weeks or 5 half-lives (whichever is shorter) must have elapsed since prior therapy that included a monoclonal antibody or checkpoint inhibitor
• Radiotherapy (XRT): 3 weeks must have elapsed since XRT; at least 6 weeks if XRT involved central nervous system (CNS) or lung fields; and at least 12 weeks from total-body irradiation (TBI), craniospinal XRT, or XRT involving ≥ 50% bony pelvis, with the exception that there is no time restriction for palliative radiation with minimal bone marrow involvement and the patient has measurable/evaluable disease outside the radiation port or the site of radiation has documented progression
• Vaccine therapy, anti-GD2 mAb therapy, or therapy with any genetically engineered T cells: Patients may have received previous vaccine therapy, anti-GD2 monoclonal antibody (mAb) therapy, or therapy with any genetically engineered T cells except prior GD2 CAR T cell therapy. At least 3 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior vaccine or monoclonal antibody therapy. At least 42 days must have elapsed since prior modified T cell, natural killer (NK) cell, or dendritic cell therapy
• Allogeneic stem cell transplant/infusion: At least 12 weeks must have elapsed since allogeneic stem cell transplant and without evidence of active graft versus host disease (GVHD)
• Autologous stem cell transplant/infusion: Patients who received an autologous stem cell infusion following myeloablative therapy should be at least 6 weeks from their infusion. Patients who received an autologous stem cell infusion following non-myeloablative therapy do not have a wash-out period; they are eligible once they meet all other eligibility requirements, including recovery from acute side effects
• Must meet parameters for apheresis per institutional guidelines. (This criterion does not apply to patients with apheresis product or usable T cell product available for use). Cryopreserved PBMCs stored from participation in other institutional cell therapy or cell collection studies or standard of care may be used to generate the cellular product on this study if they meet the criteria established in this IND
• Patients > 16 years of age must have Karnofsky >= 70%. Patients =< 16 years of age must have Lansky scale ≥ 70%; corresponding to Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Leukocytes >= 750/mcL (Patients must not be refractory to transfusions)
• Absolute neutrophil count (ANC) >= 500/mcL (Patients must not be refractory to transfusions.)

You may not qualify if…

• Receiving any other current investigational agents
• History of anaphylactic reactions attributed to anti-GD2 antibodies or to compounds of similar chemical or biologic composition to GD2CART, cyclophosphamide, fludarabine, or other agents used in this study. History of hypersensitivity to dornase alfa, Chinese hamster ovary cell products, or any of the components of pulmozyme
• Patients who require systemic corticosteroid or other immunosuppressive therapy. (A one-week washout from systemic corticosteroid or other immunosuppressive therapy is permitted.) Use of physiologic doses of corticosteroids (up to 3 mg/m\^2/day prednisone equivalent) are permitted. Use of topical, ocular, intra-articular, intra-nasal, or inhaled corticosteroids are permitted
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of additional malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless untreated and stable or disease free for at least 3 years
• Patients with central nervous system (CNS) metastases are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS.
• CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgement of the investigator may impair the ability to evaluate neurotoxicity
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled
• Ongoing infection with human immunodeficiency virus (HIV), hepatitis B (hepatitis B surface antigen [HBsAg] positive), or hepatitis C virus (anti-HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. A history of HIV, hepatitis B, or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing
• Primary immunodeficiency or history of systemic autoimmune disease (e.g., Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
• Females of childbearing potential must have a negative serum or urine pregnancy test. Pregnant females are excluded from this study because the effects of autologous GD2CART on the developing human fetus are unknown and because the chemotherapy agents used in this trial (cyclophosphamide and fludarabine) are category D agents with the potential for teratogenic or abortifacient effects. Additionally, because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with cyclophosphamide/fludarabine, breastfeeding should be discontinued if the mother is treated with cyclophosphamide/fludarabine. These potential risks may also apply to other agents used in this study
• In the investigator's judgment, unlikely to complete protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. Or in the investigator's judgment, if the patient is likely to develop significant toxicity and morbidity from CAR-T cell expansion mediated inflammation based on location of tumor site

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• National Institutes of Health Clinical Center — Bethesda, Maryland, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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