NCT06101381

CD19-directed CAR-T Cell Therapy for R/R Acute Leukemia and Lymphoma

CD19-directed CAR-T Cell Therapy for Refractory or Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma: a Multicenter Phase I/II Trial.

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 81 (estimated)
• Sponsor: University of Sao Paulo · Academic / Other
• Sex: All
• Age: 3 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The goal of this prospective, multicentric, single-arm, phase I/II clinical trial is to evaluate the safety and efficacy of a novel CD19-directed CAR-T cell locally produced in an academic institution in Brazil in patients with refractory or relapsed acute lymphoblastic leukemia or non-Hodgkin lymphoma. Participants will receive a single intravenous infusion of an autologous academic anti-CD19 CAR-T cell and will be followed for 5 years.

Detailed description

Eighty-one patients with refractory/relapsed (R/R) B acute lymphoblastic leukemia (B-ALL) or non-Hodgkin lymphoma (B-NHL) will be included in this multicentric, phase I/II clinical trial to evaluate the safety and efficacy of a novel academic CD19-directed CAR-T cell developed in Brazil. After the inclusion of the patient, lymphocyte apheresis will be performed for lymphocyte collection, followed by activation, transduction with a lentiviral vector, and expansion of produced CAR-T cells. The patient will be hospitalized and receive lymphodepleting chemotherapy started five days before CAR-T cells infusion, with cyclophosphamide (300 mg/m2/day) and fludarabine (30 mg/m2/day) for three days. On Day 0, CAR-T cells will be intravenously administered over 20-30 minutes. The optimal CAR-T cell dose will be 1,7 to 5,4 x106 cells/kg, for ALL patients, and 0,6 to 6,0 x 108 cells (total dose) for NHL patients, but any dose higher than 0,2 x 106 cells/kg (for patients \< 50 Kg) or 0,14 x 106 cells/kg and 0,1 x 108 cells (total dose) (for patients ≥ 50Kg), and lower than the maximal 2,6 x 108 cells (total dose) will be infused, depending on the obtained cellular product. During and after infusion, the patient will be monitored for signs and symptoms of toxicity and will remain hospitalized for at least two weeks. All patients will receive anti-viral and anti-pneumocystis prophylaxis. They will be monitored to evaluate treatment efficacy, and acute and late toxicities for five years after infusion.

Conditions

• Leukemia, Acute Lymphoblastic
• Lymphoma, Non-Hodgkin

Interventions

Type	Name	Description
BIOLOGICAL	CART-19	The academic CART-19 consists of autologous T lymphocytes transduced with a lentiviral vector to express a second-generation chimeric antigen receptor with a single chain variable fragment (scFv) targeting the CD19 antigen conjugated with 4-1BB co-stimulatory and CD3z signaling domains.

Timeline

• Start date: 2024-03-21
• Primary completion: 2028-12-01
• Completion: 2028-12-01
• First posted: 2023-10-26
• Last updated: 2024-12-09

Locations

5 sites across 1 country: Brazil