NeuroblastomaPhase 1NCT03721068

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

A Phase 1 study testing iC9.GD2.CAR.IL-15 T-cells, Cyclophosphamide and Fludarabine in people with Neuroblastoma and Osteosarcoma, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 months and older
Conditions the study is for: Neuroblastoma, Osteosarcoma
What is being tested?: iC9.GD2.CAR.IL-15 T-cells, Cyclophosphamide and Fludarabine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 2 sitesUnited States
Study dates: 19 Feb 2019to 19 Jun 2044
Phase: Phase 1
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 months and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Show all 17Show fewer

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
Exclusion Criteria for the Study Subjects meeting any of the following exclusion criteria will not be able to participate in this study (procurement, lymphodepletion, and cell infusion).
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.

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States2 sites, 1 recruiting

Emory - Winship Cancer Institute
Atlanta, Georgia, 30322
Withdrawn
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
Catherine Cheng, 919-445-4208, UNCImmunotherapy@med.unc.edu
Caroline Babinec, 919-962-7426, UNCImmunotherapy@med.unc.edu
Recruiting

Other trials in United States

About this study

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

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.

Read the 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 anti-GD2 antibody has been changed so that instead of floating freely in the blood, it is now joined to the T cells. However, it is unknown how long the iC9.GD2.CAR.IL-15 T cells last in the body, so their chances of fighting cancer cells are not well known.

To improve the tumor-fighting power of GD2-CAR-T cells, two additional components were added to these cells. The IL-15 gene was added so that the GD2-CAR-T cells can attack tumor cells more effectively. Interleukin-15 (IL-15) is a chemical that cells use to communicate with one another. Other research using IL-15 in combination with CAR-T cells has shown there is an increase in the body's ability to allow the CAR-T cells to survive and grow in the body. The iC9 gene was added as an "off switch" so it can stop the activity of the GD2-CAR-T cells if there are any serious bad side effects. Bad side effects seen previously in patients receiving the GD2 antibody alone include pain. In this study, the "stop switch" can be used to turn off the GD2-CAR-T cells if you experience intense pain that does not respond to normal pain treatments.

The study will enroll a minimum of 10 adult subjects and 10 pediatric subjects; all subjects will undergo lymphodepletion chemotherapy prior to the cell infusion as outlined in the protocol.

Conditions: Neuroblastoma, Osteosarcoma
Being tested: iC9.GD2.CAR.IL-15 T-cells, Cyclophosphamide, Fludarabine
Keywords: Autologous Chimeric Antigen Receptor (CAR) T Cells, Interleukin (IL)-15, Disialoganglioside (GD2), Caspase 9, Pediatric, Rimiducid, AP1903, modified T cells, CAR T
Medical subject headings: Neuroblastoma, Osteosarcoma, Gaucher Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

iC9.GD2.CAR.IL-15 T-cellsBiological
Three dose levels are being evaluated: 0.5 x 10^6, 1.0 x 10^6, 1.5 x 10^6
CyclophosphamideDrug
500 mg/m^2 IV dose on days 1-2 for lymphodepletion prior to cell infusion
FludarabineDrug
30 mg/m^2 IV dose on days 1-4 for lymphodepletion prior to cell infusion

Study groups in NCT03721068
Study group	Role	What they receive
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. Receives: Biological: iC9.GD2.CAR.IL-15 T-cells; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Feb 201919 Jun 2044

First posted26 Oct 2018
Study start19 Feb 2019
Primary completion19 May 2030 (estimated)
Study completion19 Jun 2044 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for NeuroblastomaStudies of the same condition, open and under way.
More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03721068
Sponsor's protocol ID: LCCC 1743-ATL
Other IDs: K12CA120780
Status last verified: Mar 2026
First submitted: 24 Oct 2018
Last updated: 27 Mar 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Interested in taking part?

Each site lists its own contact. Pick the site nearest to you.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Recurrent Ganglioneuroblastoma, Recurrent Neuroblastoma
Active, not recruitingObservational study
Genomic Structural Variation in Cancer Susceptibility
Breast Cancer, Colon Cancer
RecruitingPhase 2
Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors
Metastatic Chondrosarcoma, Locally Advanced Chondrosarcoma
RecruitingObservational study
Prospective Comprehensive Molecular Analysis of Endocrine Neoplasms
Endocrine Tumors, Thyroid Neoplasms
RecruitingPhase 1
PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy
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All Neuroblastoma trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03721068
Acronym / sponsor ID: LCCC 1743-ATL
Conditions: Neuroblastoma, Osteosarcoma
Keywords: Autologous Chimeric Antigen Receptor (CAR) T Cells, Interleukin (IL)-15, Disialoganglioside (GD2), Caspase 9, Pediatric, Rimiducid, AP1903, modified T cells
Phase: Phase 1
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 18 participants (estimated)
Lead sponsor: UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
Collaborators: United States Department of Defense, Bellicum Pharmaceuticals, National Cancer Institute (NCI)
Study start: 19 Feb 2019 (actual)
Primary completion: 19 May 2030 (estimated)
Study completion: 19 Jun 2044 (estimated)
First posted: 26 Oct 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The study will enroll a minimum of 10 adult subjects and 10 pediatric subjects; all subjects will undergo lymphodepletion chemotherapy prior to the cell infusion as outlined in the protocol.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
iC9.GD2.CAR.IL-15 T-cells	Experimental	Biological: iC9.GD2.CAR.IL-15 T-cells, Drug: Cyclophosphamide, Drug: FludarabineThe 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.

Who may qualify

Ages: 18 months and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (17 listed)

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:

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
iC9.GD2.CAR.IL-15 T-cellsThree dose levels are being evaluated: 0.5 x 10^6, 1.0 x 10^6, 1.5 x 10^6	Biological	iC9.GD2.CAR.IL-15 T-cells
Cyclophosphamide500 mg/m^2 IV dose on days 1-2 for lymphodepletion prior to cell infusion	Drug	iC9.GD2.CAR.IL-15 T-cells
Fludarabine30 mg/m^2 IV dose on days 1-4 for lymphodepletion prior to cell infusion	Drug	iC9.GD2.CAR.IL-15 T-cells

Primary outcome

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
Time frame: 4 weeks
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).

5 secondary outcomes

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
Time frame: 4 weeks
Expansion and persistence of iC9.GD2.CAR.IL-15 cells in vivo
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 15 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.

Related trials for Neuroblastoma

RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
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Active, not recruitingObservational study
Genomic Structural Variation in Cancer Susceptibility
Breast Cancer, Colon Cancer
RecruitingPhase 2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

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

Chapel Hill, United States

919-445-4208

UNCImmunotherapy@med.unc.edu

George Hucks, MD principal investigator

UNC Lineberger Comprehensive Cancer Center

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03721068.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.