Clinical trial NCT04429438: Multi-CAR-T Cells Targeting B Cell Lymphomas
Official title: Primary, Booster and Consolidation Multi-CAR-T Cell Therapy for the Treatment of Refractory B Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: B Cell Lymphoma (BCL)
Keywords: CAR-T
CD19
CD20
CD22
CD70
PSMA
CD13
CD79b
GD2
PMBCL
CNS-BCL
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
Collaborators: name: The Seventh Affiliated Hospital of Sun Yat-sen University
name: Shenzhen Children's Hospital
First posted: 2020-06-12
Enrollment: 11
Sex: ALL
Minimum age (years): 6
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting B cell surface molecules including CD19 and alternative CARTs as booster and consolidation treatment for patients with highly resistant B cell lymphomas, including primary mediastinal B cell lymphoma (PMBCL) and BCL involving central nervous system (CNS-BCL). Clinical response and development of a simplified and standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.

Detailed description: Chimeric antigen receptor (CAR) T cell therapy has proven effective in treating B cell malignancies. However, post CD19-CART relapses occur at high rate due to the CD19 antigen loss or the exhaustion of CART cells. Furthermore, the success of treating relapsed/refractory B cell lymphoma (BCL) such as primary mediastinal B-cell lymphoma (PMBCL) and CNS-involved BCL has been limited. To overcome tumor escape and prolong in vivo CART efficacy, we have developed a novel multiple CAR-T therapy regimen including booster and consolidation CART applications to to target highly-refractory cancer. Selected patients will be enrolled after target antigen confirmation including CD19, CD20, CD22, CD70, CD13, CD79b, GD2 and PSMA through immunostaining of their tumor specimens. The aim is to evaluate safety and long term efficacy of the multiple CART therapy strategy in the BCL patients.

Eligibility criteria: Inclusion Criteria:

1. Age older than 6 months.
2. Primary B cell lymphoma surface expression of CD19 and/or CD22/CD70/PSMA/ CD13/CD79b/GD2 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 response after treatment.
2. Bacterial, fungal, or viral 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.

Primary outcomes:
measure: Safety of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion
timeFrame: 24 weeks
Secondary outcomes:
measure: Anti tumor activity of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion
timeFrame: 1 year
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Geno-Immune Medical Institute
state: Guangdong
city: Shenzhen
country: China
facility: The Seventh Affilliated Hospital, Sun Yat-Sen University
state: Guangdong
Study officials:
References: