Blood T-Cells and EBV Specific CTLs Expressing GD-2 Specific Chimeric T Cell Receptors to Neuroblastoma Patients

NCT00085930 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 13149-NESTLESNESTLES
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Patients have high-risk neuroblastoma, a form of cancer typically found in children. The patients previously participated in a gene transfer research study using special immune cells. This research study combines two different ways of fighting disease, antibodies and T cells. Antibodies are types of proteins that protect the body from bacterial and other infections. T cells, also called cytotoxic T lymphocytes or CTLs, are special infection-fighting blood cells that can kill some tumor cells. Both antibodies and T cells have been used to treat patients with cancers and while they have shown promise, they have not been strong enough to cure most patients. The antibody used in this study is called 14g2a. This antibody sticks to neuroblastoma cells because of a substance on the outside of these cells called GD2. 14g2a and other antibodies that bind to GD2 have been used to treat people with neuroblastoma. For this study 14g2a has been changed so that instead of floating free in the blood, it is now joined to T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. T lymphocytes or CTLs can kill tumor cells but there normally are not enough of them to kill all tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the patient. Sometimes an antibody or chimeric receptor is attached to these T cells to help them bind to tumor cells. These chimeric receptor-T cells seem to kill some of the tumor, but they don't last very long in the body and so the tumor eventually comes back. We have found that T cells that are also trained to recognize the virus that causes infectious mononucleosis, Epstein Barr Virus (EBV), can stay in the blood stream for many years. By joining the 14g2a antibody to the CTLs that recognize EBV, we believe we will make a cell that can last a long time in the body (because they are EBV-specific) and recognize and kill neuroblastoma cells (because an antibody that can recognize these cells has been placed on their surface). Patients received treatment with the immune cells described above. They may want to receive an additional dose of these cells. This is being offered as an option because their neuroblastoma has returned and they have enough cells remaining to provide the patients with an additional dose. These 14g2a antibody CTLs are an investigational product not approved by the Food and Drug Administration.

Conditions

Neuroblastoma

Keywords

Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety of escalating doses of 14g2a.zeta chimeric receptor transduced autologous EBV specific cytotoxic T-lymphocytes (EBV-CTL) and 14g2a.zeta transduced autologous peripheral blood T-cells

  Listings of adverse events by patients will include the time to onset, the duration of each event, the severity of each event, and the relationship of the event to study therapy, whether it was a serious event, and whether it caused withdrawal.

  15 yrs

Secondary Outcomes (3)

• Determine the differential survival and function of these two infused cell-types in vivo, in particular to determine if chimeric receptor transduced EBV-CTLs survive longer than transduced peripheral-blood T-cells.

  15 yrs

• Determine anti-tumor effects of transduced peripheral blood T-cells and EBV specific CTLs in vivo.

  15 years

• Compare the differential survival of these infused cells in an additional 6 patients treated at dose level #1 without CD45 antibody mediated lymphodepletion, to patients previously treated at dose levels #2 and #3.

  15 years

Study Arms (1)

EBV specific CTLs w/out lymphodepletion

EXPERIMENTAL

Escalating doses of 14g2a.zeta chimeric receptor transduced autologous EBV specific cytotoxic T-lymphocytes (EBV-CTL) and 14g2a.zeta transduced autologous peripheral blood T-cells administered to patients with Neuroblastoma.

Biological: EBV specific CTLs

Interventions

EBV specific CTLs BIOLOGICAL

CTLs: 2x10e7 cells/m2

Also known as: 14g2a.zeta Chimeric Recep Transduc (EBV-CTL) w/o Lymphodepl

EBV specific CTLs w/out lymphodepletion

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• High risk neuroblastoma with a history of persistent or relapsed disease, or after initial therapy
• Patients must have a life expectancy of at least 12 weeks
• Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study
• Patients must not be currently receiving any investigational agents or have not received any tumor vaccines within the previous 6 weeks
• Patients must have an ANC \> 500, platelet count \> 20,000
• Patients who have received prior therapy with murine antibodies must have documentation of absence of human anti-mouse antibodies (HAMA) prior to enrollment on this study
• Patients must have bilirubin less than 3 times the upper limit of normal
• Patients must have AST less than 5 times the upper limit of normal
• Patients must have serum creatinine less than 3 times upper limit of normal
• Patient may not have cardiomegaly or bilateral pulmonary infiltrates on chest radiograph. Patients may have pulmonary metastatic lesions
• Patient may not have an oxygen requirement as defined by pulse oximetry of \> 90% on room air
• Patients must have Karnofsky score of \> 60% if \> 10 years old or Lansky performance score of greater than 60% if 10 years old or younger
• Patients must have autologous transduced EBV-specific CTLs and transduced peripheral blood T-cells with 15% expression or greater of 14g2a.zeta determined by flow-cytometry
• Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom
• Patients must not be pregnant or lactating

You may not qualify if:

• Patients not meeting eligibility criteria

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Li CH, Sharma S, Heczey AA, Woods ML, Steffin DHM, Louis CU, Grilley BJ, Thakkar SG, Wu M, Wang T, Rooney CM, Brenner MK, Heslop HE. Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma. Nat Med. 2025 Apr;31(4):1125-1129. doi: 10.1038/s41591-025-03513-0. Epub 2025 Feb 17.

  PMID: 39962287 DERIVED

• Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, Rossig C, Russell HV, Diouf O, Liu E, Liu H, Wu MF, Gee AP, Mei Z, Rooney CM, Heslop HE, Brenner MK. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood. 2011 Dec 1;118(23):6050-6. doi: 10.1182/blood-2011-05-354449. Epub 2011 Oct 7.

  PMID: 21984804 DERIVED

MeSH Terms

Conditions

Neuroblastoma

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

Study Officials

• Helen E Heslop, MD

  Baylor College of Medicine

  STUDY DIRECTOR

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: June 17, 2004
• First Posted: June 21, 2004
• Study Start: April 1, 2003
• Primary Completion: January 1, 2010
• Study Completion: August 1, 2025
• Last Updated: January 7, 2026

Record last verified: 2025-12

Locations

US (1)