NCT04544592

UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL

Phase I/II Dose Escalation and Preliminary Efficacy of CD19 Directed CAR-T Cells Generated Using the Miltenyi CliniMACs Prodigy System (UCD19 CAR-T) in Pediatric Patients With Relapsed and/or Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL) and B-Cell Non-Hodgkin Lymphoma (B-NHL)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 31 Days – 30 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial will investigate a new CD19 directed CAR-T therapy manufactured locally with the goals to expedite infusion to wider patient inclusion that includes those who were previously excluded, such as pediatric patients with B-cell NHL and patients in primary relapse.

Detailed description

Pediatric patients with refractory or multiply relapsed leukemia and lymphoma do poorly with traditional chemotherapy and have overall survival rates below 20%-50% depending on a variety of disease and patient related characteristics. Approximately 10-20% of pediatric patients with pre B-ALL will relapse (1) and relapsed pre B-ALL is a leading cause of cancer death in children (2). Site of relapse and timing of first relapse from initial therapy are important factors that impact the survival rates after first relapse (3). The 5-year survival for pre B-ALL pediatric patients with early relapse is 25-50% (2). Pediatric patients who experience a late relapse have excellent survival rates with chemotherapy alone, however if they have MRD positivity after reinduction, this drops their survival rates down to 50-60% (4). The FDA approval of CD19-directed CAR-T cell therapy has increased treatment options for patients with refractory disease or those in second relapse. However, many patients, including those in first relapse do not fit the current criteria to receive this treatment. As well, regardless of the number of prior relapses, some patients in second relapse cannot tolerate the extended delay and ongoing therapy that is necessary for the commercial manufacturing of these cells at the commercial level. This phase I/II trial will investigate a new CD19-directed CAR-T therapy manufactured locally with the goal of expediting the infusion to patients who were previously excluded, such as pediatric patients with relapsed B-cell NHL and patients in their initial (or greater) leukemic relapse. We hypothesize that CD19-directed CAR-T cells manufactured using the Miltenyi CliniMACs Prodigy System (UCD19 CAR-T) will be safe, well-tolerated, and show preliminary efficacy in pediatric patients with relapsed and/or refractory B-ALL or B-NHL. No controls will be used beyond historical comparisons.

Conditions

• B-cell Acute Lymphoblastic Leukemia
• B-cell Non Hodgkin Lymphoma

Interventions

Type	Name	Description
DRUG	CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells	The CD19 CAR used in this study consists of three main components: the variable regions of the anti-CD19 monoclonal antibody FMC63 71, linked to the TNFRSF-19-derived transmembrane domain, the 4-1BB costimulatory molecule, and the signaling domain of the CD3-zeta molecule. The DNA encoding this receptor was cloned into a lentiviral vector (LV) backbone.

Timeline

• Start date: 2021-03-10
• Primary completion: 2026-06-01
• Completion: 2026-07-01
• First posted: 2020-09-10
• Last updated: 2025-05-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study