Combination 4th-generation CAR-T therapy for B-cell cancers
Combination CAR-T Therapy of 4SCAR19 Plus 4SCAR20, 22, 38, 70 and 123 Targeting Hematological Malignancies
PHASE1; PHASE2 · Shenzhen Geno-Immune Medical Institute · NCT03125577
This treatment will test a combination of 4th-generation CAR-T cells that target CD19 plus one other B-cell marker in people with B-cell cancers that include both CD19-positive and CD19-negative cells.
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 (other) |
| Drugs / interventions | CAR-T, chimeric antigen receptor, CAR T, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 4 sites (Guangzhou, Guangdong and 3 other locations) |
| Trial ID | NCT03125577 on ClinicalTrials.gov |
What this trial studies
This phase I/II, multi-center interventional trial gives patients sequential or combined infusions of 4th-generation lentiviral CAR-T cells (4SCAR) targeting CD19 plus one other antigen (CD20, CD22, CD30, CD38, CD70, or CD123) after cyclophosphamide/fludarabine conditioning. The 4SCAR constructs include multiple costimulatory domains (CD28/CD137/CD27) and an inducible caspase-9 suicide switch to improve potency and safety. The trial will measure safety and clinical response while standardizing lentiviral vector and cell production across participating centers. Participants will be closely monitored for cytokine release syndrome, neurotoxicity, CAR-T persistence, and disease response.
Who should consider this trial
Good fit: Patients aged older than 6 months with B-cell malignancies expressing CD19 and at least one of the listed antigens, a Karnofsky performance score >80, hemoglobin ≥80 g/L, and ability to undergo leukapheresis and travel to a study site are the intended candidates.
Not a fit: Patients with uncontrolled bacterial/fungal/viral infections, active HIV or active HBV/HCV, pregnancy or breastfeeding, recent systemic steroids, prior failed CAR-T therapy, or other active illnesses that complicate response assessment are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, the combination could reduce relapses from CD19-negative tumor escape and increase durable remissions for patients with mixed-antigen B-cell malignancies.
How similar studies have performed: Single-antigen CD19 CAR-T therapies have achieved high remission rates but are limited by antigen-loss relapse, and multi-target or combination CAR-T approaches are experimental with encouraging early reports but not yet validated in large trials.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. age older than 6 months. 2. malignant B cell surface expression of CD19/CD20/CD22/CD30/CD38/CD70/CD123 molecules. 3. the KPS score over 80 points, and survival time is more than 1 month. 4. greater than Hgb 80 g/L. 5. no contraindications to blood cell collection. Exclusion Criteria: 1. accompanied with other active diseases, the treatment is difficult to assess patient response. 2. bacteria, fungus, or virus infection, unable to control. 3. living with HIV. 4. active HBV and HCV infection. 5. pregnant and nursing mothers. 6. under systemic steroid treatment within a week of the treatment. 7. prior failed CAR-T treatment.
Where this trial is running
Guangzhou, Guangdong and 3 other locations
- Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)
- Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)
- Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (RECRUITING)
- Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center — Kunming, Yunnan, China (RECRUITING)
Study contacts
- Principal investigator: Lung-Ji Chang, PhD — Shenzhen Geno-Immune Medical Institute
- Study coordinator: Lung-Ji Chang, PhD
- Email: c@szgimi.org
- Phone: +86 0755-86573763
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: B-cell Malignancies, 4S CAR-T, CD19, CD20, CD22, CD38, CD123, B cell leukemia