Clinical trial NCT04430530: 4SCAR-T Therapy Post CD19-targeted Immunotherapy
Official title: 4SCAR-T Therapy After Anti-CD19 Immunotherapy Targeting B Cell Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: CD19 Negative B-cell Malignancies
Keywords: 4S CAR-T CD22
4S CAR-T CD123
4S CAR-T CD38
4S CAR-T CD10
4S CAR-T CD20
CD19 Negative B cell leukemiaB-ALL
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
Collaborators: name: ShiJiaZhuang Zhongxi Children Hospital
name: Shenzhen Children's Hospital
name: The Seventh Affiliated Hospital of Sun Yat-sen University
First posted: 2020-06-12
Enrollment: 100
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 will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells (4SCAR-T) targeting CD19-negative B-ALL that express alternative surface antigens such as CD22, CD10, CD20, CD38, and CD123, as many patients relapse after anti-CD19 immunotherapy. Clinical response and optiminzation of a 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: Anti-CD19 immunotherapy based on antibody conjugated drugs or CD19-CAR-T cells has demonstrated unprecedented positive response in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, many patients still relapse and up to 30-50% of those relapses are characterized by the loss of CD19 surface antigen. Patients with CD19-negative relapse usually have a poor prognosis. The mechanisms underlying CD19-negative relapses are not fully understood and it is important to develop solutions to supplement post-CD19 immunotherapies.

Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population include many known B-cell lineage antigens. To prevent further target escape and improve the therapeutic effects, the 4th generation CAR gene-modified T cells targeting CD22, CD10, CD20, CD38, or CD123 have been considered in post anti-CD19 treatment. This study aims to evaluate safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to patients with CD19-escaped B cell malignancies.

Eligibility criteria: Inclusion Criteria:

1. Age older than 6 months.
2. B cell malignancies relapsed after anti-CD19 immunotherapy.
3. Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20.
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. 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 use within a week of the treatment.
7. Judged difficult to cooporate for continued evaluation.

Primary outcomes:
measure: Safety of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells
timeFrame: 24 weeks
Secondary outcomes:
measure: Anti-tumor activity of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells
timeFrame: 1 year
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The Seventh Affilliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Shijiazhuang
country: China
facility: Shijiazhuang Zhongxi Children Hospital
state: Hebei
Study officials:
References: