Safety and Efficacy of CD19/CD22 Dual Targeted CAR-T Cell Therapy in R/R B-Cell Acute Lymphoblastic Leukemia

Early Phase 1

• Conditions: CD19+ and CD 22+ B-ALL
• Interventions: Biological: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells; Drug: Cyclophosphamide,Fludarabine

• Registration Number: NCT05225831
• Lead Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

Brief Summary

This is an open, single-arm, prospective clinical study to evaluate the safety and efficacy of anti CD19 and CD22 CAR-T cell in the treatment of R/R B-ALL.

Detailed Description

CD19-directed CAR-T cell therapy has shown promising results in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia. CD19 and CD22 are proteins usually expressed on the surface of the B leukemia cells. The dual-CARs enables the T-cells to recognize and kill the tumor cell through recognition of CD19 and CD22.

Study Timeline

• Study Start: 2021-08-15
• Status Verified: 2022-01
• Study First Submitted: 2022-01-11
• Study First Submitted QC: 2022-01-25
• Last Update Submitted: 2022-01-25
• Study First Posted: 2022-02-07
• Last Update Posted: 2022-02-07
• Primary Completion: 2023-08
• Study Completion: 2023-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Sign the informed consent and be willing and able to comply with the visit, treatment regimen, laboratory examination and other requirements of the study as stipulated in the trial flow chart;
2. A definite diagnosis of B-cell Lymphocyte Leukemia, which meets any of the following criteria: Relapsed : a) relapsed within 12 months after first remission;Refractory: a) no remission after six weeks of induction therapy or no remission after two courses of induction therapy; b) relapsedafter CR for 2 or more times; c) The first relapse after chemotherapy and no remission after at least one salvage treatment; c) relapsed after hematopoietic stem cell transplantation;
3. ECOG Scores: 0~2
4. CD19 positive and CD22 positive were detected by immunohistochemistry or flow cytometry;
5. Estimated survival time>3 months;
6. Peripheral blood mononuclear immune cells must be collected at least 2 weeks after the last radiotherapy or systemic treatment.
7. For patients with only extramedullary recurrence of B-ALL, there must be at least one assessable lesion.

Exclusion Criteria

1. Serious cardiac insufficiency；
2. Has a history of severe pulmonary function damaging;
3. Presence of other malignant tumors.
4. Presence of active fungal, bacterial, viral, or other infection requiring IV antibiotics for management.
5. Presence of other severe autoimmune diseases or immunodeficiency disease;
6. Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]);
7. Known positive serology for human immunodeficiency virus (HIV) or syphilis。
8. Has a history of serious allergies on biological products (including antibiotics);
9. Female patients who are under pregnancy and/or lactation, or planing on pregnancy for the next 12 months.
10. Any other situations that the researchers believe will affect the results of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SL19+22 CAR-T	Cyclophosphamide,Fludarabine	Eligible patients will be treated with SL19+22 CAR-T.
SL19+22 CAR-T	Autologous CD19/CD22 Chimeric Antigen Receptor T-cells	Eligible patients will be treated with SL19+22 CAR-T.

Primary Outcome Measures

Name	Time	Method
Safety: Incidence of adverse events	up to 28 days	To evaluate the possible adverse events that could occurred within the first month post SL19+22 infusion, including symptoms such as cytokine release syndrome and neurotoxicity.
Efficacy: Remission Rate	Up to 3 months	Remission Rate includes complete remission(CR)、CR with incomplete blood count recovery(CRi)、No remission(NR)

Secondary Outcome Measures

Name	Time	Method
Efficacy:duration of response (DOR)	24 months post CAR-T cells infusion	Duration of response
Efficacy: progression-free survival (PFS)	24 months post CAR-T cells infusion	progression-free survival (PFS) time
CAR-T proliferation	3 months post CAR-T cells infusion	the copy number of CD19 and CD22 CAR- T cells in the genomes of peripheral blood mononuclear cell (PBMC) by quantitative Real-time PCR (qPCR).
Cytokine release	First month post CAR-T cells infusion	Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry

Trial Locations

Locations (1)

Hebei Yanda Ludaopei Hospital; 🇨🇳 Langfang, Hebei, China