Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma

NCT03721068 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: LCCC 1743-ATLK12CA120780
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

The body has different ways of fighting infections and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are molecules that fight infections and protect your body from diseases caused by bacteria and toxic substances. Antibodies work by sticking to those bacteria or substances, which stops them from growing and causing bad effects. T cells are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been enough to cure most patients. This multicenter study is designed to combine both T cells and antibodies in order to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells (CAR) cells targeted against the disialoganglioside (GD2) antigen that express Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9), also known as iC9.GD2.CAR.IL-15 T cells.

Conditions

Neuroblastoma; Osteosarcoma

Keywords

Autologous Chimeric Antigen Receptor (CAR) T Cells; Interleukin (IL)-15; Disialoganglioside (GD2); Caspase 9; Pediatric; Rimiducid; AP1903; modified T cells; CAR T

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events as a measure of safety and tolerability of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma or relapsed/refractory osteosarcoma

  Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (AEs) (CTCAE, version 5.0), a descriptive terminology which can be utilized for AE reporting. A grading (severity) scale is provided for each AE term/symptom: Grade 1 (Mild; asymptomatic); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE). Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).

  4 weeks

Secondary Outcomes (5)

• Identify the maximum tolerated dose (MTD) of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma or relapsed/refractory osteosarcoma

  4 weeks

• Expansion and persistence of iC9.GD2.CAR.IL-15 cells in vivo

  15 years

• Anti-tumor response rate to iC9.GD2.CAR.IL-15 t cell administration in pediatric subjects with relapsed or refractory neuroblastoma per Revised International Neuroblastoma Response Criteria (INCR) or relapsed/refractory osteosarcoma by RECIST v1.1

  6 weeks

• Overall survival (OS) in pediatric subjects with relapsed or refractory neuroblastoma or relapsed/refractory osteosarcoma treated with iC9.GD2.CAR.IL-15 T cells

  15 years

• Progression free survival (PFS) in pediatric subjects with relapsed or refractory neuroblastoma or relapsed/refractory osteosarcoma treated with iC9.GD2.CAR.IL-15 T cells

  15 years

Study Arms (1)

iC9.GD2.CAR.IL-15 T-cells

EXPERIMENTAL

The continuous reassessment method (CRM) will be used to estimate the maximum-tolerated dose (MTD) of cells that to be given in dose escalation cohorts comprised of 2-6 subjects. The final MTD will be the dose with estimated probability of dose limiting toxicity (DLT) closest to the target toxicity rate of 20%. Three cell doses will be evaluated: 0.5 x 10\^6 cells/kg, 1.0 x 10\^6 cells/kg, 1.5 x 10\^6 cells/kg. Cohort enrollment will be staggered and each subject must complete at least 2 weeks of the cell treatment without incident of DLT before another subject can be enrolled at that dose level. A minimum of two subjects must complete the 4-week post-infusion DLT period before enrollment at the next higher dose level will be considered. If dose level 1 is determined to be above a tolerable dose, de-escalation would occur to dose level -1 where subjects would receive 0.25 x 10\^6 cells/kg.

Biological: iC9.GD2.CAR.IL-15 T-cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

iC9.GD2.CAR.IL-15 T-cells BIOLOGICAL

Three dose levels are being evaluated: 0.5 x 10\^6, 1.0 x 10\^6, 1.5 x 10\^6

iC9.GD2.CAR.IL-15 T-cells

Cyclophosphamide DRUG

500 mg/m\^2 IV dose on days 1-2 for lymphodepletion prior to cell infusion

iC9.GD2.CAR.IL-15 T-cells

Fludarabine DRUG

30 mg/m\^2 IV dose on days 1-4 for lymphodepletion prior to cell infusion

iC9.GD2.CAR.IL-15 T-cells

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written HIPAA authorization signed by legal guardian.
• Adequate performance status as defined by Lansky or Karnofsky performance status of ≥ 60 (Lansky for \<16 years of age).
• Life expectancy ≥12 weeks.
• Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma, confirmation of osteosarcoma at diagnosis
• High-risk neuroblastoma with persistent/refractory or relapsed disease, defined as:
• First or greater relapse of neuroblastoma following completion of aggressive multi-drug frontline therapy.
• First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy. Persistent/refractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).
• Patients must be diagnosed with high risk neuroblastoma at initial diagnosis or if non-high risk at time of initial diagnosis must have had evidence of metastatic progression when \>18 months of age as defined in the protocol or relapsed or refractory osteosarcoma that is not responsive to standard treatment.
• Measurable or evaluable disease per Revised INRC for subjects with neuroblastoma or measurable disease by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 criteria for subjects with osteosarcoma.
• Adequate central nervous system function as defined by:
• No known Central Nervous System ( CNS) disease
• No seizure disorder requiring antiepileptic drug therapy

You may not qualify if:

• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Has a known additional malignancy that is active and/or progressive requiring treatment.
• History of hypersensitivity reactions to murine protein-containing products.
• History of hypersensitivity to cyclophosphamide or fludarabine.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• United States Department of Defense: collaborator
• Bellicum Pharmaceuticals: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Emory - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

WITHDRAWN

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma; Gaucher Disease

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• George Hucks, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 26, 2018
• Study Start: February 19, 2019
• Primary Completion (Estimated): May 19, 2030
• Study Completion (Estimated): June 19, 2044
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (2)