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Trial record 1 of 1 for:    NCT05262673
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NGS-MRD Assessment of Combination Immunotherapies Targeting B-ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05262673
Recruitment Status : Recruiting
First Posted : March 2, 2022
Last Update Posted : March 8, 2022
Information provided by (Responsible Party):
Shenzhen Geno-Immune Medical Institute

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

Condition or disease Intervention/treatment Phase
B-Cell Acute Lymphoblastic Leukemia Biological: Antigen-specific T cells CART/CTL and DCvac Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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)

  2. Clinical response [ Time Frame: 1 year ]
    Leukemia blast cells are detected by multiparameter flow cytometry, and MRD is measured by IgH NGS.

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age older than 6 months.
  2. High-burden (≥30% blast cells) B-ALL tumor specimen for clonal IgH identification and CTL/DC vac preparation is required
  3. Expression of CD19, CD22, CD20, CD10 or CD123 is determined in malignant cells by flow cytometry or immuno-histochemical staining.
  4. Karnofsky performance status (KPS) score is higher than 60 and life expectancy > 3 months.
  5. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5x upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3x upper limit of normal, total bilirubin ≤ 2.0mg/dL.
  6. No cell separation contraindications.
  7. Abilities to understand and the willingness to provide written informed consent.

Exclusion Criteria:

  1. Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
  2. Active bacterial, fungal or viral infection not controlled by adequate treatment.
  3. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  4. Pregnant or nursing women may not participate.
  5. History of glucocorticoid for systemic therapy within the week prior to entering the test.
  6. Previously treatment with any gene therapy products.
  7. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Information from the National Library of Medicine

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 identifier (NCT number): NCT05262673

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Contact: Lung-Ji Chang, Ph.D 86-0755-86725195

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China, Guangdong
Shenzhen Geno-Immune Medical Institute Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, Ph.D    86-0755-86725195   
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
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Responsible Party: Shenzhen Geno-Immune Medical Institute Identifier: NCT05262673    
Other Study ID Numbers: GIMI-IRB-22001
First Posted: March 2, 2022    Key Record Dates
Last Update Posted: March 8, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shenzhen Geno-Immune Medical Institute:
DC vaccine
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases