Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL

Description

PRIMARY OBJECTIVE:

* To examine the feasibility of manufacture and administration of autologous CD19 CAR T cells at a minimum target dose of 0.3 x 10^6 to 1 x 10^6 per kilogram for patients <50 kg and a flat dose of 0.3 – 1 x 10^8 for patients ≥50 kg using the Miltenyi CliniMACS Prodigy automated T Cell Transduction (TCT) process.
* To evaluate the safety of administration of CD19 CAR T cells after lymphodepletion with fludarabine and cyclophosphamide.

SECONDARY OBJECTIVE:

• To estimate the efficacy of CD19 specific CAR-T cells in pediatric and young adult patients with relapsed/refractory CD19+ B-cell ALL and NHL.

EXPLORATORY OBJECTIVE:

• To evaluate the persistence of CD19 CAR T cells after infusion.

The autologous lymphocytes are collected from the patient via apheresis. The apheresis product is then transported to the on-site GMP facility for manufacture of the CAR T cell product. Patients may be admitted to begin lymphodepleting chemotherapy during the CAR T cell manufacturing process. When the CAR T cell product is ready, the cells may be administered fresh or may be cryopreserved for use at a later date depending on the patient's clinical status.

All patients will be admitted to the hospital to undergo a Fludarabine/Cyclophosphamide based leukoreduction conditioning regimen to be completed 2-14 days prior to CAR T cell infusion. Patients will be admitted for a minimum of 7 days after the CAR T infusion to monitor for toxicity including cytokine release syndrome, neurologic toxicity, and tumor lysis syndrome.

Lymphodepleting chemotherapy:

* Fludarabine 30 mg/m2/day IV x 4 days
* Cyclophosphamide 500 mg/m2/day IV x 2 days

CD19 CAR T cell dose:

* 0.3 x 10^6 to 1 x 10^6 per kilogram for patients <50 kg
* Flat dose of 0.3 – 1 x 10^8 for patients ≥50 kg