NCT06709469

Phase I Clinical Trial of CART Cell Therapy for Refractory/Relapsed Acute Lymphoblastic Leukemia in Children, Adolescents and Young Adults

A Phase I Clinical Trial of CART Cell Therapy for Refractory/ Relapsed Acute Lymphoblastic Leukemia With Unmet Needs in Children, Adolescents and Young Adults: Feasibility and Safety Study (REALL_CART).

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Instituto de Investigación Hospital Universitario La Paz · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to test the feasibility and safety of an academic production of two different anti-CD19 chimeric antigen receptor T cells (CART) products according to the different biomarkers of the disease in children and young adults with relapsed/refractory CD19+ B cell acute lymphoblastic leukemia (r/r B-ALL) or relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). The main questions it aims to answer are: 1. The safety and feasibility of autologous CART-19/22 in children, adolescents and young adults with a CD19+/- CD22+ relapse/ refractory disease for a r/r B-ALL. 2. The safety and feasibility of allogeneic CART-NKG2D (chimeric-antigen receptor Natural-killer group 2, member D) in children, adolescents and young adults with r/r T-ALL.

Detailed description

Incredible progress has been made in the treatment of relapsed/refractory CD19+ acute lymphoblastic leukemia (r/r ALL) by the application of anti-CD19 chimeric antigen receptor (CAR) T cells (CART19). However, equivalent progress has not been achieved in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL). Furthermore and although the majority of patients with CD19+ r/r ALL respond to CART19, 30-60% of patients relapse after this treatment, probably due to the short persistence of CAR T-cells and the immune escape or down-regulation of CD19 antigen. Patients with relapsed ALL after CART19 have a very poor prognosis and novel treatment approaches are urgently needed. To date, both relapse after CART19 malignancies and T-ALL represent an unmet medical need where no effective or targeted therapies currently exist. Recently, we and other groups have reported how T-ALL and acute myeloid leukemia (AML) cell lines were more sensitive to CART-NKG2D (chimeric-antigen receptor Natural-killer group 2, member D) cytotoxicity than B-ALL cell lines. We have previous experience in the production and administration, under compassionate use, of CART cells targeting dual CD19/CD22 antigens and NKG2D ligands. In this context, this phase I clinical trial is designed to test the feasibility and safety of an academic production of two different CART products according to the different biomarkers of the disease. In the present study (ReALL\_CART), we propose an umbrella design methodology using autologous dual CART-19/22 for CD19+/-CD22+/- relapse after CART19 or allogeneic CART-NKG2D for NKG2DL+ r/r T-ALL.

Conditions

• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	Autologous CD19/CD22 CAR T cells	A total of two doses of autologous CD19/CD22 CAR T cells (first dose of up to 0.75x106/kg fresh cells), and a second infusion of unfrozen cells (same dose) if there has been no ≥ grade 1 cytokine-release syndrome (CRS) in the next 72 h; intravenously.
BIOLOGICAL	Allogeneic CART-NKG2D cells	A total of up to 3x106/kg allogeneic CART-NKG2D cells divided in three doses of up to 1x106/kg will be infused; intravenously. First infusion of fresh cells, and the 2nd and 3rd infusion of unfrozen cells (same dose) if there has been no ≥ grade 1 CRS (every 48 hours).

Timeline

• Start date: 2025-07-08
• Primary completion: 2030-06-01
• Completion: 2030-12-01
• First posted: 2024-11-29
• Last updated: 2025-09-22

Locations

1 site across 1 country: Spain