NGS-MRD Assessment of Combination Immunotherapies Targeting T-ALL
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|ClinicalTrials.gov Identifier: NCT05277753|
Recruitment Status : Recruiting
First Posted : March 14, 2022
Last Update Posted : March 15, 2022
|Condition or disease||Intervention/treatment||Phase|
|T-Cell Acute Lymphoblastic Leukemia||Biological: Antigen-specific T cells CAR-T/CTL and DCvac||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NGS-MRD Evaluation of Antigen-specific T Cells and DC Vaccine Combination Targeting T-cell Acute Lymphoblastic Leukemia|
|Estimated Study Start Date :||March 15, 2022|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2025|
|Experimental: CART/CTL/DCvac cells to treat T-ALL||
Biological: Antigen-specific T cells CAR-T/CTL and DCvac
Antigen-specific T cells CAR-T/CTL and DCvac cells to treat T-ALL
- Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria. [ Time Frame: 1 year ]Safety of infusion
- Clinical response [ Time Frame: 1 year ]Leukemia blast cells are detected by multiparameter flow cytometry
- Evaluate the percentage of minimal leukemia residue in bone marrow [ Time Frame: 1 year ]Minimal leukemia residue（MRD）is measured by TCR next generation sequencing（NGS）.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05277753
|Contact: Lung-Ji Chang, Ph.Demail@example.com|
|Shenzhen Geno-immune Medical Institute||Recruiting|
|Shenzhen, Guangdong, China, 518000|
|Contact: Lung-Ji Chang, ph.D 86-0755-86725195 firstname.lastname@example.org|