B Cell Malignancies
Conditions
Keywords
CAR-T, B cell Malignancies, CD19, CD22
Brief summary
The purpose of this study is to assess the feasibility, safety and efficacy of anti-CD19/22 bi-specific CAR-T cell therapy in patients with CD19 and/or CD22 positive B cell malignancies. Another goal of the study is to learn more about the safety and function of the anti-CD19/22 bi-specific CAR-T cells and their persistency in patients.
Detailed description
Important Regulatory Notice: This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China. ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities. 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-CD19/22 bi-specific CAR (bi-4SCAR-CD19/22). The CAR molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD19 or CD22, which is expressed at high levels on tumor cells but not at significant levels on normal tissues. To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific CD19/22 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 CD22 positive cancer patients.
Interventions
BIOLOGICALbi-4SCAR CD19/22 T cells
Infusion of bi-4SCAR CD19/22 T cells at 10\^6 cells/kg body weight via IV
Sponsors
Shenzhen Geno-Immune Medical Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 75 Years
Healthy volunteers
No
Inclusion criteria
1. age older than 6 months. 2. malignant B cell surface expression of CD19 or CD22 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 CD22 CAR-T treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of fourth generation bi-4SCARCD19/22 T cells in patients with B cell malignancies | 24 weeks | Safety of fourth generation bi-4SCARCD19/22 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti tumor activity of fourth generation bi-4SCARCD19/22 T cells in patients with relapsed or refractory B cell malignancies | 1 year | scale of CAR copies and leukemic cell burden (for efficacy) |
Countries
China
Contacts
CONTACTLung-Ji Chang, PhD
Outcome results
None listed