Recruiting
Phase 1

GINAKIT with Etanercept

Sponsor:

Baylor College of Medicine

Code:

NCT03294954

Conditions

Neuroblastoma

Eligibility Criteria

Sex: All

Age: 1 - 21

Healthy Volunteers: Not accepted

Interventions

GINAKIT Cells

GINAKIT cells + Etanercept

Study Details

Brief summary:

This research study combines two different ways of fighting cancer: antibodies and Natural Killer T cells (NKT). Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special white blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. In a previous clinical trial, investigators made artificial genes called a chimeric antigen receptors (CAR), from an antibody called 14g2a that recognizes GD2, a molecule found on almost all neuroblastoma cells (GD2-CAR). Investigators put these genes into the patients' own T cells and gave them back to patients that had neuroblastoma.

NKT cells are another special subgroup of white blood cells that can specifically go into tumor tissue of neuroblastoma. Inside the tumor, there are other white blood cells called macrophages which help the cancer cells to grow and recover from injury. NKT cells can specifically kill these macrophages and slow the tumor growth.

We will expand NKT cells and add GD2-specific chimeric antigen receptors to the cells. We think these cells might be better able to attack NB since they also work by destroying the macrophages that allows the tumor to grow. The chimeric antigen receptor will also contain a gene segment to make the NKT cells last longer. This gene segment is called CD28. In addition, to further improve the antitumor activity of the GINAKIT cells we added another gene expressing a molecule called Interleukin -15 (IL-15). The combination of these 3 components showed the most antitumor activity by CAR expressing NKT cells and improved these cells' survival in animal models. We also found that a medicine called ETANercept can slow down neuroblastoma growth, which might enhance the effects of the modified cells. In this part of our study, we aim to treat children with hard-to-treat neuroblastoma using these modified NKT cells along with ETANercept. Though ETANercept has been used to treat other diseases, such as rheumatoid arthritis in children, there is limited information about the safety, efficacy, and risk of ETANercept treatment in combination with cellular therapies.

GD2-CAR expressing NKTs have not been tested in patients so far. The purpose of this study is to find the largest effective and safe dose of GD2-CAR NKT cells (GINAKIT cells), to evaluate their effect on the tumor and how long they can be detected in the patient's blood and what affect they have on the patient's neuroblastoma.

Conditions

Neuroblastoma

Study ID

NCT03294954

Start date

Jan 18, 2018

Status verified date

Sep, 2025

Completion date

Aug 10, 2040

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1 - 21

Healthy Volunteers: Not accepted

Procurement Inclusion Criteria:

1. Relapsed or refractory high risk neuroblastoma
2. Life expectancy of at least 12 weeks
3. Age greater than 1 year and less than 21 years old
4. Karnofsky/Lansky score of 60% or greater
5. Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies)
6. Ability to tolerate leukocyte apheresis
7. Informed consent and assent (as applicable) obtained from parent/guardian and child.
8. Patients must have an ANC greater than or equal to 500/µl, platelet count greater than or equal to 20,000/µl. Patients may be transfused to obtain a platelet count greater than or equal to 20,000/µl.
9. Pulse Ox greater than or equal to 90% on room air
10. Serum AST less than 3 times the upper limit of normal
11. Total Bilirubin less than 1.5 times the upper limit of normal
12. Creatinine < 1.5 times the upper limit of normal
13. Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
14. Weight greater than 12kg
15. Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to procurement

Procurement Exclusion Criteria:

1. Rapidly progressive disease
2. History or hypersensitivity to murine protein-containing products
3. Tumor causing airway obstruction
4. Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine
5. Severe previous toxicity from cyclophosphamide or fludarabine based on the enrolling physician's assessment
6. HIV infection
7. History of hypersensitivity, anaphylaxis, and/or adverse event with Etanercept

Treatment Inclusion Criteria:

1. Relapsed or refractory high risk neuroblastoma
2. Life expectancy of at least 12 weeks
3. Age greater than 1 year and less than 21 years old
4. Karnofsky/Lansky score of 60% or greater
5. Patients must have an ANC greater than or equal to 500/µl, platelet count greater than or equal to 20,000/µl. Patients may be transfused to obtain a platelet count greater than or equal to 20,000/µl.
6. Pulse Ox greater than or equal to 90% on room air
7. Serum AST less than 3 times the upper limit of normal
8. Total Bilirubin less than 1.5 times the upper limit of normal
9. Creatinine < 1.5 times the upper limit of normal
10. Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria and expected to tolerate lymphodepletion).
11. Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies
12. Patients must have autologous transduced NKTs with greater than or equal to 20% expression of GD2-specific CAR.
13. Informed consent and assent (as applicable) obtained from parent/guardian and child.
14. Weight greater than 12kg
15. Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to the start of LD

Treatment Exclusion Criteria:

1. Rapidly progressive disease
2. Currently receiving any investigational drugs
3. History or hypersensitivity to murine protein-containing products
4. Cardiomegaly or bilateral pulmonary infiltrates on chest radiograph or CT. However, patients with cardiomegaly on imaging may be enrolled if they have an assessment of cardiac function (i.e., ECHO or MUGA) within 3 weeks of starting protocol therapy that is within normal limits. Additionally, patients with bilateral pulmonary infiltrates on imaging may be enrolled if the lesions are not consistent with active neuroblastoma (i.e., negative on functional imaging with PET or MIBG, or by pathologic assessment).
5. Tumor potentially causing airway obstruction
6. Pregnancy or lactation or not willing to use birth control
7. Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine
8. Severe previous toxicity form cyclophosphamide or fludarabine based on the enrolling physician's assessment
9. HIV infection
10. History of hypersensitivity, anaphylaxis, and/or adverse event with Etanercept

Study Design

Enrollment

70 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: GINAKIT cells

GINAKIT cells will be administer to patients with Neuroblastomas on Day 0.

experimental: Experimental: GINAKIT cells + Etanercept.

GINAKIT cells will be administer to patients with Neuroblastomas on Day 0 in combination of Etanercept.

Interventions

GINAKIT Cells

Six dose levels of GINAKIT cells will be studied. Dosing will be based on the actual number of transduced cells. All doses are per m2.

  • Dose Level 1 = 3 x 10\^6
  • Dose Level 2 = 1 x 10\^7
  • Dose Level 3 = 3 x 10\^7
  • Dose Level 4 = 1 x 10\^8
  • Dose Level 5 = 3 x 10\^8
  • Dose Level 6 = 1 x 10\^9

GINAKIT cells + Etanercept

Four dose levels of GINAKIT cells in combination of Etanercept will be studied. Dosing will be based on the actual number of transduced cells. All doses are per m2.

  • Combination Dose level 1: 3 x 10\^6 + Etanercept\*
  • Combination Dose level 2: 1 x 10\^7 + Etanercept\*
  • Combination Dose level 3: 3 x 10\^7 + Etanercept\*
  • Combination Dose level 4: 1 x 10\^8 + Etanercept

Primary outcome measure

  • Maximum tolerated dose of autologous NKTs expressing a 2nd generation GD2-specific chimeric antigen receptor administered to patients with relapsed or refractory neuroblastoma in combination with Etanercept. [ Time Frame: 28 days ]

Central Contacts and Locations

Central contacts

Gengwen Tian, MD

832-454-2642gxtian1@texaschildrens.org

Ramy Sweidan

832-824-4234rxsweida@texaschildrens.org

Locations

Texas Children's Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

Andras Heczey, MD

832-824-4233axheczey@txch.org

More Information

Sponsor

Baylor College of Medicine

Last update posted

Sep 19, 2025

Last verified

Sep, 2025

Keywords

  • Neuroblastoma
  • Natural Killer T-Cells
  • Chimerical Antigen Receptor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Baylor College of Medicine on 2025-09-19.