NCT05277753

NGS-MRD Assessment of Combination Immunotherapies Targeting T-ALL

NGS-MRD Evaluation of Antigen-specific T Cells and DC Vaccine Combination Targeting T-cell Acute Lymphoblastic Leukemia

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Shenzhen Geno-Immune Medical Institute · Academic / Other
• Sex: All
• Age: 6 Months – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the feasibility, safety, and efficacy of a combination therapy in the treatment of T-cell acute lymphoblastic leukemia (T-ALL): multi-antigen-targeted chimeric antigen receptor T cells (CAR-T) followed by engineered immune effector cytotoxic T cells (CTLs) and immune modified dendritic cell vaccine (DCvac). This approach is aimed to achieve NGS MRD negativity in T-ALL patients, which can identify a very low risk of relapse and define patients with possible long-term remission without further treatment.

Detailed description

Minimal residual disease (MRD) monitoring is currently performed in T-ALL patients to evaluate treatment response and define risk stratification. Patients with good prognosis have undetectable MRD levels after treatment, while persistent MRD defines high relapse-risk patients. The standardized flow cytometry assay detects MRD reliably in bone marrow or peripheral blood at levels ≥0.01% mononuclear cells. More sensitive MRD assay detecting specific clonal T cell receptors (TCR) by next-generation sequencing (NGS) can reliably detect blasts at levels ≤10-6 cells. Given the high sensitivity, NGS-MRD approach improves distinction between deeply negative and very low positive cases. Recent studies also demonstrate that NGS-MRD assessment of the bone marrow with undetectable blast cells is a strong predictive factor, indicating patients with possible long-term response after CAR-T cell therapy. Acute lymphoblastic leukemia (ALL) is hematological malignancy with the highest incidence in children and adolescents. After standardized treatment, the survival rate is relatively high. ALL is divided into two types: B cells and T cells, the latter accounting for about 15% of childhood leukemias and about 25% of adult leukemias. Compared with children and adolescents with B-lineage ALL (B-ALL), T-ALL is extremely aggressive, and patients are prone to early disease recurrence, and in the event of recurrence, event-free survival (EFS) and overall survival (OS) are lower, at less than 25%, even with more intensive treatment, which might require further combination therapy to enhance anti-tumor immunity and eradicate all malignant cells. Therefore, this protocol includes multi-target CAR-T cell infusions followed by antigen-specific cytotoxic T lymphocyte (CTL)-based immunotherapy, which is based on T cells reacting with specific T-ALL tumor antigens and immune-modified dendritic cells (DCvac) fused with T leukemic cells as DC vaccines. In addition to the significant success of CAR-T cell therapy, various clinical studies also reported the importance and potential benefits of using tumor-specific T cells in different types of cancer. Moreover, DC-based vaccines as another agent of immunotherapy have proven to prevent or delay relapse in leukemia patients achieving remission. In this study, we combine those strategies to augment anti-tumor immunity in patients and expect undetectable NGS-MRD, a long-lasting remission to prevent disease recurrence. We propose a novel protocol which combines multi-CAR-T cell therapy, engineered immune effector CTLs and DCvac against T-ALL. The aim of this study is to evaluate the feasibility, safety, and efficacy of the NGS-MRD analysis-based combinational immunotherapy.

Conditions

• T-Cell Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Antigen-specific T cells CAR-T/CTL and DCvac	Antigen-specific T cells CAR-T/CTL and DCvac cells to treat T-ALL

Timeline

• Start date: 2022-03-15
• Primary completion: 2024-12-31
• Completion: 2025-12-31
• First posted: 2022-03-14
• Last updated: 2022-03-15

Locations

1 site across 1 country: China