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Clinical Trial NCT03721068 for Neuroblastoma, Osteosarcoma is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here.
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Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma Phase 1 18

Recruiting
Clinical Trial NCT03721068 is designed to study Treatment for Neuroblastoma, Osteosarcoma. It is a Phase 1 interventional study that is recruiting, having started on February 19, 2019, with plans to enroll 18 participants. Led by UNC Lineberger Comprehensive Cancer Center, it is expected to complete by June 19, 2044. The latest data from ClinicalTrials.gov was last updated on March 27, 2026.
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...Show More
Detailed Description
In previous studies, it has been shown that when T cells have part of an antibody attached to them, they are better at recognizing and killing cancer cells. The antibody that will be used in this study is called anti-GD2. This antibody floats around in the blood and can detect and stick to cancer cells called neuroblastoma cells because they have a substance on the outside of the cells called GD2. For this study, the...Show More
Official Title

A Phase I Study of Autologous Activated T-Cells Expressing a 2nd Generation GD2 Chimeric Antigen Receptor, IL-15, and iCaspase9 Safety Switch Administered To Patients With Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma

Conditions
NeuroblastomaOsteosarcoma
Other Study IDs
NCT ID Number
NCT03721068
Start Date (Actual)
2019-02-19
Last Update Posted
2026-03-27
Completion Date (Estimated)
2044-06-19
Enrollment (Estimated)
18
Study Type
Interventional
PHASE
Phase 1
Status
Recruiting
Keywords
Autologous Chimeric Antigen Receptor (CAR) T Cells
Interleukin (IL)-15
Disialoganglioside (GD2)
Caspase 9
Pediatric
Rimiducid
AP1903
modified T cells
CAR T
Primary Purpose
Treatment
Design Allocation
N/A
Interventional Model
Single Group
Masking
None (Open Label)
Arms / Interventions
Participant Group/ArmIntervention/Treatment
ExperimentaliC9.GD2.CAR.IL-15 T-cells
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. Cohor...Show More
iC9.GD2.CAR.IL-15 T-cells
Three dose levels are being evaluated: 0.5 x 10\^6, 1.0 x 10\^6, 1.5 x 10\^6
Cyclophosphamide
500 mg/m\^2 IV dose on days 1-2 for lymphodepletion prior to cell infusion
Fludarabine
30 mg/m\^2 IV dose on days 1-4 for lymphodepletion prior to cell infusion
Primary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
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 Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
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
Tolerability of iC9.GD2.CAR.IL-15 T cells will be assessed by NCI-CTCAE criteria and the CRS grading criteria outlined in Section 12.4 and neurotoxicity/ICANS will be graded according to criteria outlined in Section 12.5
4 weeks
Expansion and persistence of iC9.GD2.CAR.IL-15 cells in vivo
Persistence of iC9.GD2.CAR.IL-15 T cells in vivo will be determined by quantitative Polymerase chain reaction (PCR) and flow cytometry in peripheral blood samples
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
The overall response rate (ORR = complete (CR) + partial (PR) + minor (MR) responses) to iC9.GD2.CAR.IL-15 T cell infusion will be determined using the revised International Neuroblastoma Response Criteria (INRC) for subjects with neuroblastoma. The overall response rate (ORR = complete (CR) + partial (PR) responses) for subjects with osteosarcoma will be measured using Response evaluation criteria in solid tumors (RECIST) version 1.1
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
OS will be measured from the date of administration of iC9.GD2.CAR.IL-15 T cells to the date of death
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
PFS is defined from the date of administration of iC9.GD2.CAR.IL-15 T cells to the date of signs and symptoms of treatment failure or relapse from CR or PR, or death from any cause.
15 years
Participation Assistant
Eligibility Criteria

Eligible Ages
Child, Adult, Older Adult
Minimum Age
18 Months
Eligible Sexes
All
All clinical and laboratory data required for determining eligibility must be available in the subject's medical/research record which will serve as the source document.

Because of the nature of iC9.GD2.CAR.IL-15 T cell product preparation, subjects will be assessed for initial study enrollment eligibility (prior to cell procurement) and then will have to meet criteria prior to starting lymphodepletion and prior to T cell infusion.

  1. Written HIPAA authorization signed by legal guardian.

  2. Adequate performance status as defined by Lansky or Karnofsky performance status of ≥ 60 (Lansky for <16 years of age).

  3. Life expectancy ≥12 weeks.

  4. Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma, confirmation of osteosarcoma at diagnosis

  5. High-risk neuroblastoma with persistent/refractory or relapsed disease, defined as:

    1. First or greater relapse of neuroblastoma following completion of aggressive multi-drug frontline therapy.
    2. 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).
    3. 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.

  6. 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.

  7. Adequate central nervous system function as defined by:

    1. No known Central Nervous System ( CNS) disease
    2. No seizure disorder requiring antiepileptic drug therapy

  1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  2. Has a known additional malignancy that is active and/or progressive requiring treatment.
  3. History of hypersensitivity reactions to murine protein-containing products.
  4. History of hypersensitivity to cyclophosphamide or fludarabine.
UNC Lineberger Comprehensive Cancer Center logoUNC Lineberger Comprehensive Cancer Center
No contact data.
2 Study Locations in 1 Countries

Georgia

Emory - Winship Cancer Institute, Atlanta, Georgia, 30322, United States
Withdrawn

North Carolina

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina, 27599-7295, United States
Catherine Cheng, Contact, 919-445-4208, [email protected]
Caroline Babinec, Contact, 919-962-7426, [email protected]
George Hucks, MD, Principal Investigator
Recruiting