Fourth-generation CAR‑T therapy targeting CD22, CD123, CD38, CD10, CD20, or TSLPR for CD19‑negative B‑ALL

CART Immunotherapy Targeting CD19 Negative Acute Lymphoblastic Leukemia

This treatment will try fourth‑generation CAR‑T cells that target CD22, CD123, CD38, CD10, CD20, or TSLPR in people with B‑cell acute lymphoblastic leukemia who have lost CD19 after prior CD19 CAR‑T therapy or who lack CD19 expression.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 6 Months to 75 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (Academic / other)
• Drugs / interventions: CAR-T, immunotherapy, CART, chimeric antigen receptor
• Locations: 3 sites (Guangzhou, Guangdong and 2 other locations)
• Trial ID: NCT04016129 on ClinicalTrials.gov

What this trial studies

This multi-center phase I/II trial will administer one or multiple non‑CD19 fourth‑generation CAR‑T cell products using a standardized lentiviral vector and cell production protocol to patients with CD19‑negative B‑cell malignancies. Eligible patients must have leukemic blasts expressing one or more of CD22, CD123, CD38, CD10, CD20, or TSLPR and adequate performance status and laboratory values. The study will monitor safety, adverse events, and clinical responses and will collect manufacturing and durability data on the CAR‑T products. Sites are in China and the protocol includes procedures for leukapheresis, CAR‑T manufacturing, lymphodepletion, infusion, and post‑infusion follow‑up.

Who should consider this trial

Good fit: Ideal candidates are patients aged over 6 months with native CD19‑negative B‑cell malignancy or relapse after CD19 CAR‑T therapy whose malignant cells express one or more of CD22, CD123, CD38, CD10, CD20, or TSLPR and who have adequate performance status and lab values for cell collection and infusion.

Not a fit: Patients unlikely to benefit include those whose leukemia does not express any of the listed target antigens, or those with uncontrolled active infections, HIV/HBV/HCV, pregnancy or nursing, recent systemic steroid use, or other conditions that preclude safe participation.

Why it matters

Potential benefit: If successful, this approach could provide effective anti‑leukemic control for patients with CD19‑negative relapse by targeting alternative B‑cell antigens and reduce the chance of further antigen‑escape relapses.

How similar studies have performed: CD19 CAR‑T has produced dramatic remissions and CD22‑targeted CAR‑T has shown activity in CD19‑negative relapse, but multi‑antigen fourth‑generation CAR‑T approaches are relatively new and less extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age older than 6 months.
2. Native CD19 negative B cell malignancies or relapse after CD19-CAR-T immunotherapy.
3. Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20/TSLPR.
4. The KPS score over 80 points, and survival time is more than 1 month.
5. Greater than Hgb 80 g/L.
6. No contraindications to blood cell collection.

Exclusion Criteria:

1. Complications with other active diseases, and difficult to assess patient response.
2. Bacteria, fungus, or virus infection, and unable to control.
3. Living with HIV.
4. Active HBV and HCV infection.
5. Pregnant and nursing mothers.
6. Under systemic steroid use within a week of the treatment.

Where this trial is running

Guangzhou, Guangdong and 2 other locations

• Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (Recruiting)
• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (Recruiting)
• Zhongxi Children Hospital — Shijiazhuang, Hebei, China (Recruiting)

Study contacts

• Principal investigator: Lung-Ji Chang, PhD — Shenzhen Geno-Immune Medical Institute
• Study coordinator: Lung-Ji Chang, PhD

Conditions B-cell Leukemia; CD19- B-ALL; CART; CD22, CD123, CD38, CD10, CD20, TSLPR