CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL

NCT ID: NCT05470777

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-19
• Study Completion Date: 2039-07-21

Brief Summary

Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CAR-T has been a major issue. Multi-antigen CAR T and combination with other regimens may reduce the relapse rate. The investigators first conducted CD22/CD19 CAR T-cells and auto-HSCT "sandwich " strategy as consolidation therapy in patients with B-ALL. The main Purpose of this study was to observe the safety and efficacy of this new strategy.

Detailed Description

The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5*10^6/kg respectively,CAR-T1) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Standard BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT(CAR-T2). Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.

Conditions

B-cell Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CD22/CD19 CAR T and auto-HSCT sandwich strategy as consolidation therapy for B-ALL

Group Type: EXPERIMENTAL

CD22/CD19 CAR T and auto-HSCT "sandwich" strategy

Intervention Type: COMBINATION_PRODUCT

The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5\*10\^6/kg respectively) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Modified BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.

Interventions

CD22/CD19 CAR T and auto-HSCT "sandwich" strategy

The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5\*10\^6/kg respectively) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Modified BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• subjects with a primary diagnosis of B-ALL who have any of the following: (a) no suitable allogeneic HSCT donor. (b) refusal of allogeneic HSCT.
• positive expression of CD19 and CD22 in peripheral blood or bone marrow primary cells detected by flow cytometry.
• cardiac ultrasound left ventricular ejection fraction ≥ 50%; Creatinine ≤ 1.6 mg/dl; alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the normal range and total bilirubin ≤ 2.0 mg/dl; Pulmonary function ≤ grade 1 dyspnea (CTCAE v5.0) with oxygen saturation > 91% without oxygenation.
• subjects aged 15-65 years (including 15 and 65 years), regardless of gender.
• T-cell amplification test pass.
• expected survival > 3 months.

Exclusion Criteria

• patients with recurrence of only isolated extramedullary lesions.
• combination of other malignant tumors.
• previously treated with anti-CD19 or/and CD22 or/and CD3 therapies.
• immunosuppressants use within 2 weeks prior to signing informed consent or plan to immunosuppressants after signing informed consent.
• uncontrolled active infections.
• HIV infection.
• active hepatitis B or hepatitis C infection.
• history of severe tachyphylaxis to aminoglycoside antibiotics.
• history or presence of clinically relevant Central Nervous System (CNS) pathology, such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Natural Science Foundation of China(Grant No. 81970138)

UNKNOWN

Sponsor Role: collaborator

Jiangsu Province Natural Science Foundation of China (Grant No. BK20210091)

UNKNOWN

Sponsor Role: collaborator

Jining Medical University

OTHER

Sponsor Role: collaborator

The Second People's Hospital of Huai'an

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Bengbu Medical University

OTHER

Sponsor Role: collaborator

Northern Jiangsu People's Hospital

OTHER

Sponsor Role: collaborator

Affiliated Hospital of Nantong University

OTHER

Sponsor Role: collaborator

Suzhou Hospital of Traditional Chinese Medicine

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Sheng-Li Xue, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Sheng-Li Xue, M.D.

Role: CONTACT

slxue@suda.edu.cn

+86 512 67781139

Facility Contacts

Sheng-Li Xue, M.D.

Role: primary

slxue@suda.edu.cn

+86 512 6778 1139

Other Identifiers

SZCART02

Identifier Type: -

Identifier Source: org_study_id