Combination immunotherapy for treating B-cell acute lymphoblastic leukemia

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

This study is testing a new combination treatment for people with B-cell acute lymphoblastic leukemia to see if it can help them achieve a low risk of relapse and stay in remission longer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 6 Months to 65 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, immunotherapy
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT05262673 on ClinicalTrials.gov

What this trial studies

This study evaluates the feasibility, safety, and efficacy of a combination therapy for B-cell acute lymphoblastic leukemia (B-ALL) using multi-antigen-targeted chimeric antigen receptor T cells (CAR-T), followed by engineered immune effector cytotoxic T lymphocytes (CTLs) and an immune-modified dendritic cell vaccine (DCvac). The goal is to achieve minimal residual disease (MRD) negativity, indicating a low risk of relapse and the potential for long-term remission without further treatment. The study employs next-generation sequencing (NGS) for more sensitive MRD monitoring, which can detect very low levels of residual disease. This innovative approach aims to enhance anti-tumor immunity and eradicate malignant cells in patients who have not fully responded to CAR-T therapy alone.

Who should consider this trial

Good fit: Ideal candidates are patients over 6 months old with high-burden B-ALL and specific antigen expression in their malignant cells.

Not a fit: Patients with severe illness or medical conditions that prevent protocol management may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve long-term remission rates for patients with B-ALL.

How similar studies have performed: Other studies have shown promising results with CAR-T therapies, but this specific combination approach is novel and untested.

Eligibility criteria

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.

Where this trial is running

Shenzhen, Guangdong

• Shenzhen Geno-Immune Medical Institute — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Lung-Ji Chang, Ph.D

Conditions B-Cell Acute Lymphoblastic Leukemia; B-ALL; CAR T; CTL; DC vaccine