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

Phase 2

Recruiting

• Conditions: B-cell Acute Lymphoblastic Leukemia

• Registration Number: NCT05470777
• Lead Sponsor: The First Affiliated Hospital of Soochow University

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.

Study Timeline

• Study Start: 2020-01-19
• Study First Submitted: 2022-07-20
• Study First Submitted QC: 2022-07-20
• Study First Posted: 2022-07-22
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-30
• Last Update Posted: 2025-06-05
• Primary Completion: 2026-07-21
• Study Completion: 2039-07-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 37

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	2 years	It is measured from the date of the first CAR-T (CAR-T 1) to the date of death from any cause; subjects not known to have died at last follow-up are censored on the date they were last known to be alive

Secondary Outcome Measures

Name	Time	Method
Leukemia-free survival (LFS)	2 years	It is measured from the date of achievement of a remission after CAR-T 1 until the date of relapse from CR, or CRi, or death from any cause; subjects not known to have any of these events are censored on the date they were last examined.
Measurable residual disease (MRD) negative rate and duration	2 years	MRD is detected by flow cytometry (FC-MRD) and second-generation gene sequencing of IgH rearrangement (NGS-MRD) after the first CAR-T (CAR-T 1) . FC-MRD negative is defined as MRD\<10-4 and NGS-MRD negative is defined as MRD\<10-6.
Incidence of adverse events (AEs)	2 years	AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0) after the first CAR-T (CAR-T 1) .

Trial Locations

Locations (1)

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China