NCT03594162

Compassionate Use of CAR T Cells Targeting the CD19 Antigen and Containing the Inducible Caspase 9 Safety Switch

Compassionate Use Administration of Autologous CAR T Cells Targeting the CD19 Antigen and Containing the Inducible Caspase 9 Safety Switch

• Status: No Longer Available
• Phase: —
• Study type: Expanded Access
• Enrollment: —
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 3 Years – 70 Years
• Healthy volunteers: —

Summary

This protocol for compassionate use combines 2 different ways of fighting disease: antibodies and T cells. Both antibodies and T cells have been used to treat patients with cancers, and both have shown promise, but neither alone has been sufficient to cure most patients. This protocol combines both T cells and antibodies to create a more effective treatment. The investigational treatment is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD19 antigen (ATLCAR.CD19) administration. Prior studies have shown that a new gene can be put into T cells and will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes a piece of an antibody called anti-CD19. This antibody sticks to leukemia cells because they have a substance on the outside of the cells called CD19. For this protocol, the anti-CD19 antibody has been changed so that instead of floating free in the blood part of it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD19 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown. Preliminary results have shown that many subjects receiving this treatment have experienced unwanted side effects including cytokine release syndrome. In this protocol, to help reduce cytokine release syndrome symptoms, the ATLCAR.CD19 cells have a safety switch that when active, can cause the cells to become dormant. These modified ATLCAR.CD19 cells with the safety switch are referred to as iC9-CAR19 cells. If the patient experiences moderate to severe cytokine release syndrome as a result of being given iC9-CAR19 cells, the patient can be given a dose of a second study drug, AP1903, if standard interventions fail to alleviate the symptoms of cytokine release syndrome. AP1903 activates the iC9-CAR19 safety switch, reducing the number of the iC9-CAR19 cells in the blood. The primary purpose of this protocol is to treat a single patient with a second dose of iC9-CAR19 T cells.

Detailed description

Lymphodepleting Chemotherapy: The patient will receive a lymphodepleting regimen of fludarabine 25 mg/m2/day administered IV over 30 min for three consecutive days and a single IV dose of cyclophosphamide 900 mg/m2 administered over 1 hr on the fourth day. Administration of iC9-CAR19 T cells: Post lymphodepletion, if the patient meets eligibility criteria for cellular therapy, then will receive iC9-CAR19 T cells within 2-14 days after completing the pre-conditioning chemotherapy regimen. We will administer iC9-CAR19 post lymphodepletion at one of the following doses based on the percentage of circulating lymphoblasts prior to lymphodepletion: (1) dose of 5 x 10\^5 transduced cells/kg or (2) dose of 1 x 10\^5 transduced cells/kg. Duration of Therapy: Therapy under this compassionate use protocol involves 1 infusion of iC9-CAR19 cells. Duration of Follow-up: The patient will be followed for up to 15 years for replication-competent retrovirus evaluation or until death, whichever occurs first.

Conditions

• Acute Lymphoblastic Leukemia
• Immune System Diseases
• Immunoproliferative Disorders

Interventions

Type	Name	Description
DRUG	iC9-CAR19 cells	One of two dose levels will be given: 1 x 10\^5 or 5 x 10\^5
DRUG	AP1903	Subjects who develop grade 4 CRS or grade 3 CRS that is refractory to standard of care interventions will be given AP1903 at .4 mg/kg.
DRUG	Cyclophosphamide	900 mg/m\^2 IV over 1 hour on day 4 of lymphodepleting chemotherapy.
DRUG	Fludarabine	25 mg/m\^2/day IV over 30 minutes administered for 3 consecutive days.

Timeline

• First posted: 2018-07-20
• Last updated: 2021-12-03

Locations

1 site across 1 country: United States