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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05436496
Other study ID # GIMI-IRB-22008
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date June 30, 2022
Est. completion date June 30, 2026

Study information

Verified date June 2022
Source Shenzhen Geno-Immune Medical Institute
Contact Lung-Ji Chang, PhD
Phone 86-0755-86725195
Email c@szgimi.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to assess the feasibility, safety and efficacy of CD19/70 bi-specific CAR-T cell therapy in patients with CD19 and/or CD70 positive B cell malignancies. Another goal of the study is to learn more about the safety and function of the anti-CD19/70 bi-specific CAR-T cells and their persistency in patients.


Description:

Patients with refractory and/or recurrent B cell malignancies have poor prognosis despite complex multimodal therapy. Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Further, more than 40% patients with progressive large B cell lymphoma (LBCL) experienced reduced or lost expression of CD19 on the tumor cells after CAR19 treatment; low surface CD19 density before treatment was associated with progressive disease. Therefore, novel curative approaches are needed. The investigation attempts to use genetically modified T cells to express a 4th generation lentiviral anti-CD19/70 bi-specific CAR (bi-4SCAR-CD19/70). The CAR molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD19 or CD70, which is expressed at high levels on tumor cells but not at significant levels on normal tissues. CD70 is highly expressed in many cancers, but limited in normal tissues, it is a potential CAR-T therapeutic target. Expression of CD70 was observed on multiple tumor types including solid tumor as well as B cell malignancies. In addition, it has been reported that anti-CD70 CAR T-cells can eliminate CD70-positive cells and exhibit strong anti-tumor effects in preclinical animal models. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibited a higher affinity and antitumor effect against CD70-positive tumor cells. A potential strategy to prevent relapse due to antigen escape is to infuse T-cells capable of recognizing multiple antigens. To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific CD19/70 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory B cell cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in CD19 and/or CD70 positive cancer patients.


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date June 30, 2026
Est. primary completion date December 31, 2025
Accepts healthy volunteers No
Gender All
Age group 6 Months to 75 Years
Eligibility Inclusion Criteria: 1. age older than 6 months. 2. malignant B cell surface expression of CD19 or CD70 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 and difficult to assess patient response. 2. bacterial, fungal, or viral infection, unable to control. 3. living with HIV. 4. active HBV or HCV infection. 5. pregnant and nursing mothers. 6. under systemic steroid treatment within a week of the treatment. 7. prior failed CD19 and CD70 CAR-T treatment.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
bi-4SCAR CD19/70 T cells
Infusion of bi-4SCAR CD19/70 T cells at 10^6 cells/kg body weight via IV

Locations

Country Name City State
China Shenzhen Geno-immune Medical Institute Shenzhen Guangdong

Sponsors (1)

Lead Sponsor Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety of fourth generation bi-4SCARCD19/70 T cells in patients with B cell malignancies Safety of fourth generation bi-4SCARCD19/70 T cells in patients with B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events standard to evaluate the level of adverse events 12 weeks
Secondary Anti-tumor activity of fourth generation bi-4SCARCD19/70 T cells in patients with relapsed or refractory B cell malignancies Scale of CAR copies (for efficacy) 1 year
Secondary Anti-tumor activity of fourth generation bi-4SCARCD19/70 T cells in patients with relapsed or refractory B cell malignancies Scale of leukemic cell burden (for efficacy) 1 year
See also
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Recruiting NCT05432882 - CD19/22 Bi-specific CAR-T Cell Therapy Phase 1/Phase 2
Terminated NCT00672152 - A Phase I Study of WT1 Peptides to Induce Anti-Leukemia Immune Responses Following Transplantation Phase 1
Recruiting NCT06375161 - Anti-CD19-CAR-T Cells in Relapsed/Refractory B-cell Tumor Patients. Early Phase 1
Recruiting NCT05618028 - Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets Phase 1