Ignite Creation Date:
2025-12-24 @ 4:11 PM
Ignite Modification Date:
2026-03-01 @ 8:56 PM
Study NCT ID:
NCT04539366
Status:
SUSPENDED
Last Update Posted:
2025-11-03
First Post:
2020-09-04
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
GD2-CAR PERSIST: Production and Engineering of GD2-Targeted, Receptor Modified T Cells (GD2CART) for Osteosarcoma or Neuroblastoma to Increase Systemic Tumor Exposure
Status:
SUSPENDED
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Other - review of safety data
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the feasibility of producing T cells modified to express a GD2-specific chimeric antigen receptor (GD2-CAR-expressing autologous T-lymphocytes \[GD2CART\]) meeting established release criteria using a dasatinib containing culture platform and retroviral vector in the Miltenyi CliniMACS Prodigy (Registered Trademark) system.
II. Determine the safety and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) via administration of escalating doses of autologous GD2CART in children and young adults with relapsed/refractory osteosarcoma and neuroblastoma following cyclophosphamide-fludarabine based lymphodepletion.
III. Determine clinical activity in a preliminary fashion of autologous GD2CART in children and young adults with relapsed, refractory osteosarcoma and neuroblastoma.
SECONDARY OBJECTIVES:
I. Measure persistence of adoptively transferred GD2CART and correlate this with antitumor effects.
II. If unacceptable toxicity occurs that is possibly, probably, or definitely related to GD2CART, assess the capacity for rimiducid (AP1903), a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.
III. Describe the feasibility and tolerability of a second infusion of GD2CART in select patients.
EXPLORATORY OBJECTIVES:
I. Compare persistence of GD2CART administered in this trial to that observed in a previous trial using GD2.OX40.28.z.iCasp9 CAR T cells (NCI 14-C-0059) and assess features of the T cell product and the expanded T cells in vivo that correlate with persistence.
II. Conduct exploratory studies measuring levels of circulating myeloid cells including myeloid derived suppressor cells (MDSCs) in patients treated on this trial and compare levels to those observed in NCI 14-C-0059.
III. Explore GD2 expression in patients with neuroblastoma and osteosarcoma, including patients who have previously received anti-GD2 antibodies, from tissue and/or bone marrow samples at study entry and if available, after cell infusion.
OUTLINE: This is a dose-escalation study of GD2CART followed by a dose-expansion study.
LYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (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 echocardiogram (ECHO), multigated acquisition scan (MUGA) or cardiac magnetic resonance imaging (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.
After completion of study treatment, patients are followed up three times weekly until day 14, twice weekly until day 28, at months 2, 3, 6, 9, and 12, every 3 months until the end of the second year, then annually for up to 10 years.
I. Determine the feasibility of producing T cells modified to express a GD2-specific chimeric antigen receptor (GD2-CAR-expressing autologous T-lymphocytes \[GD2CART\]) meeting established release criteria using a dasatinib containing culture platform and retroviral vector in the Miltenyi CliniMACS Prodigy (Registered Trademark) system.
II. Determine the safety and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) via administration of escalating doses of autologous GD2CART in children and young adults with relapsed/refractory osteosarcoma and neuroblastoma following cyclophosphamide-fludarabine based lymphodepletion.
III. Determine clinical activity in a preliminary fashion of autologous GD2CART in children and young adults with relapsed, refractory osteosarcoma and neuroblastoma.
SECONDARY OBJECTIVES:
I. Measure persistence of adoptively transferred GD2CART and correlate this with antitumor effects.
II. If unacceptable toxicity occurs that is possibly, probably, or definitely related to GD2CART, assess the capacity for rimiducid (AP1903), a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.
III. Describe the feasibility and tolerability of a second infusion of GD2CART in select patients.
EXPLORATORY OBJECTIVES:
I. Compare persistence of GD2CART administered in this trial to that observed in a previous trial using GD2.OX40.28.z.iCasp9 CAR T cells (NCI 14-C-0059) and assess features of the T cell product and the expanded T cells in vivo that correlate with persistence.
II. Conduct exploratory studies measuring levels of circulating myeloid cells including myeloid derived suppressor cells (MDSCs) in patients treated on this trial and compare levels to those observed in NCI 14-C-0059.
III. Explore GD2 expression in patients with neuroblastoma and osteosarcoma, including patients who have previously received anti-GD2 antibodies, from tissue and/or bone marrow samples at study entry and if available, after cell infusion.
OUTLINE: This is a dose-escalation study of GD2CART followed by a dose-expansion study.
LYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (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 echocardiogram (ECHO), multigated acquisition scan (MUGA) or cardiac magnetic resonance imaging (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.
After completion of study treatment, patients are followed up three times weekly until day 14, twice weekly until day 28, at months 2, 3, 6, 9, and 12, every 3 months until the end of the second year, then annually for up to 10 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2020-06646 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| PED-CITN-02 | OTHER | Pediatric Early Phase Clinical Trial Network | View | |
| PED-CITN-02 | OTHER | CTEP | View | |
| U24CA224309 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA154967 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA228823 | NIH | None | https://reporter.nih.gov/quic… | View |