NGS-MRD Assessment of Combination Immunotherapies Targeting B-ALL
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|ClinicalTrials.gov Identifier: NCT05262673|
Recruitment Status : Recruiting
First Posted : March 2, 2022
Last Update Posted : March 8, 2022
|Condition or disease||Intervention/treatment||Phase|
|B-Cell Acute Lymphoblastic Leukemia||Biological: Antigen-specific T cells CART/CTL and DCvac||Phase 1|
Minimal residual disease (MRD) monitoring is currently performed in B-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. A 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 immunoglobulin heavy (IgH) chain rearrangement by next-generation sequencing (NGS) can approach reliably detectable blast level at ≤10-6 cells. Given the high sensitivity, the 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.
In the past decade, adoptively transferred T cells modified with chimeric antigen receptors (CARs) have demonstrated high effectiveness and changed the treatment paradigm for B-ALL. More than 80% B-ALL patients achieved complete remission due to CAR-T treatment, but some patients with CR still have MRD that ultimately leads to relapse, which indicates the importance for further combination therapy to enhance anti-tumor immunity and to eradicate all malignant cells. Therefore, this protocol includes multi-target CAR-T cell infusions followed by cytotoxic T lymphocyte (CTL)-based immunotherapy, which react with B-ALL tumor antigens, and then followed by injection of immune-modified dendritic cells fused with leukemic cells (DCvac). In addition to the significant success of CAR-T cell therapy, various clinical studies also reported the importance and potential benefits of using engineered tumor-specific T cells in different types of cancer. Moreover, DC-based vaccine as another agent of immunotherapy has proven to prevent or delay relapse in leukemia patients achieving remission. In this study, we propose to combine those strategies to augment anti-tumor immunity in patients and expect undetectable NGS-MRD remission to prevent disease recurrence.
We propose a novel protocol which combines multiple CAR-T cell therapy, engineered immune effector CTLs and DCvac against B-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 B-cell Acute Lymphoblastic Leukemia|
|Estimated Study Start Date :||March 1, 2022|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2025|
|Experimental: CART/CTL/DCvac cells to treat B-ALL||
Biological: Antigen-specific T cells CART/CTL and DCvac
Antigen-specific T cells CAR-T/CTL and DCvac cells to treat B-ALL
- Safety of infusion [ Time Frame: 1 year ]Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria and physiological parameters (for safety, measuring cytokine response, fever, symptoms)
- Clinical response [ Time Frame: 1 year ]Leukemia blast cells are detected by multiparameter flow cytometry, and MRD is measured by IgH 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): NCT05262673
|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|