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

Acute Lymphoblastic Leukemia, in Relapse Clinical Trial

Official title: Safety and Feasibility of On-Site Manufacture of CD19 CAR T Cells Using the CliniMACS Prodigy in Pediatric and Young Adult Patients With Relapsed/Refractory CD19 Positive Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma

Status Not yet recruiting

Clinical Trial Summary

This pilot study examines the safety and efficacy of anti-CD19 CAR T cells manufactured on-site in children and young adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma.

Patients will undergo screening, leukapheresis (cell collection), lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by the anti-CD19 CAR T cell infusion. The lymphodepleting chemotherapy is administered over four days IV to prepare the body for the CAR T cells. The anti-CD19 CAR-T cells are infused between 2-14 days after the last dose of chemotherapy. This study is designed for participants to begin lymphodepleting chemotherapy during the CAR T cell manufacture and receive a fresh cell infusion on the day that manufacturing is complete. Some patients may need more time in between the cell collection and the CAR T cell infusion, therefore, the cells may be manufactured and frozen prior to administration. Patients will be followed for a year after the cell infusion on the study and for up to 15 years to monitor for potential long term side effects of cell therapy.

Clinical Trial 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 ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia With Failed Remission
• Acute Lymphoblastic Leukemia, in Relapse
• B Cell Leukemia
• B-cell Non Hodgkin Lymphoma
• Leukemia
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma Refractory
• Non-Hodgkin's Lymphoma, Relapsed
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT05779930
• Study type: Interventional
• Source: Nationwide Children's Hospital
• Contact: Clelie Peck
• Phone: 614-722-5634
• Email: clelie.peck@nationwidechildrens.org
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: April 2024
• Completion date: December 2027