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Cyclophosphamide

Fludarabine

Fludarabine phosphate

Acetaminophen

Diphenhydramine

Promethazine

Leukopharesis: cells collected with a target of ≥1 x10\^9 TNC with ≥3% CD3+ cells.

Lymphodepleting chemotherapy: 4 days of IV chemotherapy with fludarabine and cyclophosphamide.

* Fludarabine 30 mg/m2/day IV x 4 days (days -6 through -3)
* Cyclophosphamide 500 mg/m2/day IV x 2 days (days -6 and-5)

anti-CD19 CAR T cells:

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

The cell infusion will take place on day 0 (at least 2 days after completion of lymphodepleting chemotherapy). The patient will receive pre-medication with acetaminophen and diphenhydramine 30-60 minutes prior to the cell infusion.

Infusion of CD19 CAR-T Cells manufactured on-site using the CliniMACS Prodigy

CD19 specific Chimeric Antigen Receptor T Cell

Clelie Peck

Margaret Lamb, MD

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.

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

A single-arm, unblinded, pilot treatment study

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

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

Reported as the proportion of products successfully manufactured and infused

Proportion of patients achieving a response at 1 month post infusion

Complete response rate at 1 month post infusion

Best overall response (complete response, partial response, stable disease, progressive disease)

MRD status at 30 days post infusion will be presented with descriptive statistics. MRD will be performed utilizing both flow cytometry and NGS.

Overall survival and event free survival will be assessed using the Kaplan-Meier method. Survival will be measured as the time from cell infusion to event or censoring.

Nationwide Children's Hospital

Assistant Professor of Pediatrics

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL	NCT05779930	Acute Lymphobla... Non-Hodgkin's L... Non-Hodgkin's L... Acute Lymphobla... B-cell Non Hodg... B Cell Leukemia	CD19 specific C...	- 30 Years	Nationwide Children's Hospital
Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL	NCT05779930	Acute Lymphobla... Non-Hodgkin's L... Non-Hodgkin's L... Acute Lymphobla... B-cell Non Hodg... B Cell Leukemia	CD19 specific C...	- 30 Years	Nationwide Children's Hospital
Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL	NCT05779930	Acute Lymphobla... Non-Hodgkin's L... Non-Hodgkin's L... Acute Lymphobla... B-cell Non Hodg... B Cell Leukemia	CD19 specific C...	- 30 Years	Nationwide Children's Hospital

Spots Global Cancer Trial Database for cd19 specific chimeric antigen receptor t cell