3RD GENERATION GD2 SPECIFIC CHIMERIC ANTIGEN RECEPTOR TRANSDUCED AUTOLOGOUS NATURAL KILLER T-CELLS FOR NEUROBLASTOMA

• Status: Withdrawn
• Trial end date: 2030-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This research study is for patients that have a cancer called Neuroblastoma that has either come back after treatment or did not respond to the standard medicines used to treat it. This study combines two different ways of fighting cancer: antibodies and Natural Killer T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting 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. The 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, the investigators made a gene called a chimeric antigen receptor (CAR), from an antibody called 14g2a that recognizes GD2, a molecule found on almost all neuroblastoma cells (GD2-CAR). They put this gene into the patients' own T cells and gave them back to patients that had neuroblastoma. Nineteen patients were treated on that study and there were no long term side-effects seen after the GD2 T cell infusion. As the investigators have followed the patients over time, they noticed that for those patients with disease at the time of their infusion, the time to progression (the amount of time it takes before their neuroblastoma got worse) was longer in those whom they could find GD2 T cells in the blood for more than 6 weeks after the last T cell infusion. Because of this, the investigators think that if effector cells are able to last longer, they may have a better chance of killing neuroblastoma tumor cells.

Natural Killer T cells are a special subset of innate lymphocytes that can effectively go into tumor tissues of neuroblastoma. Inside the tumor, there are certain white blood cells which help the cancer cells to grow and recover from injury. Natural Killer T-cells can specifically kill these cells. In this study, Natural Killer T cells will be genetically engineered to express GD2-CAR to attack neuroblastoma cells and the white blood cells inside the tumor tissue.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Alex's Lemonade Stand Foundation; Center for Cell and Gene Therapy, Baylor College of Medicine; Texas Children's Hospital
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

Procurement Inclusion Criteria:

• High risk neuroblastoma or persistent or relapsed disease

• Life expectancy of at least 12 weeks

• Age ≥1 and ≤18 years old

• Karnofsky/Lansky score of 60% or greater

• Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies)

• Ability to tolerate leukocyte apheresis

• Informed consent for leukocyte apheresis

• Informed consent and assent (as applicable) obtained from parent/guardian and child.

Procurement Exclusion Criteria:

• Rapidly progressive disease

• History of hypersensitivity to murine protein containing products

Treatment Inclusion Criteria:

• High risk neuroblastoma with persistent or relapsed disease

• Life expectancy of at least 12 weeks

• Age ≥1 and ≤18 years old

• Karnofsky/Lansky score of 60% or greater

• Patients must have an ANC ≥ 500 without the use G-CSF or GM-CSF for at least 48hrs, platelet count ≥ 20,000

• Pulse Ox ≥ 90% on room air

• AST less than 5 times the upper limit of normal

• Bilirubin less than 3 times the upper limit of normal

• Serum creatinine less than 3 times upper limit of normal

• Recovered from the acute toxic effects of all prior chemotherapy (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).

• Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies

• Patients must have autologous transduced NKTs with greater than or equal to 20% expression of GD2-specific CAR.

• Informed consent and assent (as applicable) obtained from parent/guardian and child.

Treatment Exclusion Criteria:

• Rapidly progressive disease

• Currently receiving other investigational drugs

• History of hypersensitivity to murine protein containing products

• History of 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).

• Evidence of tumor potentially causing airway obstruction

• Patients who are pregnant, lactating, or unwilling to use birth control

• Patients currently receiving immunosuppressive drugs such as corticosteroids(Patients may receive treatment if treated with corticosteroids with dose of less than 0.5mg/kg/day of prednisone equivalent), tacrolimus or cyclosporine.

• Patients who have previously experienced severe toxicity from cyclophosphamide and fludarabine.

• All labs must be collected within 10 days prior to initiation of study related treatment (except for verification of GD2 transduction)