Study Stopped
Other - review of safety data
Testing a New Immune Cell Therapy, GD2-Targeted Modified T-cells (GD2CART), in Children, Adolescents, and Young Adults With Relapsed/Refractory Osteosarcoma and Neuroblastoma, The GD2-CAR PERSIST Trial
GD2-CAR PERSIST: Production and Engineering of GD2-Targeted, Receptor Modified T Cells (GD2CART) for Osteosarcoma or Neuroblastoma to Increase Systemic Tumor Exposure
5 other identifiers
interventional
67
1 country
6
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2022
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 4, 2020
CompletedFirst Posted
Study publicly available on registry
September 7, 2020
CompletedStudy Start
First participant enrolled
January 25, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2040
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2040
May 4, 2026
April 1, 2026
18.9 years
September 4, 2020
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Feasibility of producing GD2-CAR-expressing autologous T-lymphocytes (GD2CART) cells
Success will be defined by manufacturing and expansion of GD2CART to satisfy the targeted dose level and meet the requirements of the Certificate of Analysis. Specifically, dose escalation will proceed if 3 or more of the first 3 to 6 patients in a dose level are able to produce adequate cells for evaluation.
Up to day 28 days after cell infusion
Incidence of adverse events (AEs)
Safety of GD2CART will be by the incidence and severity of dose limiting toxicities, treatment emergent AEs, serious adverse events, laboratory abnormalities, changes in vital signs, and changes in physical examination following infusion of GD2CART cells.
Up to 15 years
Maximum tolerated dose
Estimate of the maximum tolerated dose of autologous GD2CART in children and young adults with relapsed/refractory osteosarcoma and neuroblastoma following cyclophosphamide-fludarabine based lymphodepletion defined as the dose at which less than 33% of evaluable patients experience a cycle 1 dose limiting toxicity.
Up to day 28 days after cell infusion
Best response to GD2CART cells
Simon's two stage design will be used to evaluate the clinical benefit of GD2CART after conditioning lymphodepletion chemotherapy in two groups of patients: children and young adults with recurrent, refractory osteosarcoma and neuroblastoma.
Up to day 28 days after cell infusion
Secondary Outcomes (3)
Persistence of GD2CART cells
Up to 5 years
Capacity for rimiducid (AP1903) to reverse unacceptable toxicity related to GD2CART administration
Up to 28 days after cell infusion
Feasibility and tolerability of a second infusion of GD2CART cells
After a 2nd infusion of GD2CART cells
Other Outcomes (3)
Persistence of GD2CART cells
Up to 15 years
Biomarkers
Up to 28 days after cell infusion
GD2 expression
Up to 28 days after cell infusion
Study Arms (1)
Treatment (GD2 CAR T)
EXPERIMENTALLYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate IV daily on days -5 to -2 and cyclophosphamide IV daily on days -4 to -2. GD2CART: Patients receive GD2CART cells IV on day 0. Patients also undergo ECHO, MUGA or cardiac MRI scan during screening, blood sample collection throughout the trial, and tumor biopsies and bone marrow aspiration and biopsy as clinically indicated. In addition, patients undergo standard imaging scans throughout the trial.
Interventions
Undergo collection of blood
Undergo bone marrow biopsy
Given IV
Given IV
Given IV
Undergo standard imaging scans
Undergo cardiac MRI
Undergo MUGA
Eligibility Criteria
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)
- 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
- 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
- I-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
- +28 more criteria
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
- Untreated central nervous system (CNS) metastasis. Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are permitted. Patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities without specific therapy, are permitted. Patients with asymptomatic subcentemeric CNS lesions are permitted if no immediate radiation or surgery is indicated
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rosandra N Kaplan
Cancer Immunotherapy Trials Network
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 4, 2020
First Posted
September 7, 2020
Study Start
January 25, 2022
Primary Completion (Estimated)
December 31, 2040
Study Completion (Estimated)
December 31, 2040
Last Updated
May 4, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.