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NCT06985498

PHASE2

Immunotherapy Combined With Auto-HSCT and CD22/CD19 CAR-T Sandwich Strategy for B-ALL

Sponsor: The First Affiliated Hospital of Soochow University

View on ClinicalTrials.gov

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. We conduct pre-auto-HSCT immunotherapy to achieve MRD negative remission, then perform auto-HSCT followed by CD22/CD19 CAR-T "sandwich " strategy in AYA and adult patients with B-ALL. The main Purpose of this study was to observe the safety and efficacy of this new strategy.

Official title: Safety and Efficacy of Pre-Auto-HSCT Immunotherapy Combined With Auto-HSCT Followed by the CD22/CD19 CAR-T Sandwich Strategy for AYA and Adult B-cell Acute Lymphoblastic Leukemia

Key Details

Gender

All

Age Range

15 Years - 65 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-06-01

Completion Date

2029-09-01

Last Updated

2026-03-24

Healthy Volunteers

Conditions

Acute Lymphobkastic Leukemia

Interventions

COMBINATION_PRODUCT

Sandwich stratergy

Newly diagnosed patients first receive standard chemotherapy as induction therapy, followed by immunotherapies as consolidation therapy. Relapsed or refractory patients directly receive immunotherapies. Minimal Residual Disease （MRD）was evaluated by multicolor flow cytometry （MFC-MRD）and next-generation sequencing of IgH rearrangement （NGS-MRD）after immunotherapies. Immunotherapies includes CD19-directed CD3 T-cell engager, inotuzumab ozogamicin (INO) and CD22/CD19 CAR-T cell. In principle, these three treatment options are administered sequentially. Once patients achieve dual negativity of MFC-MRD and NGS-MRD, no further immunotherapies are applied, and patients proceed to autologous stem cell mobilization and collection. Prior to autologous stem cell transplantation (Auto-HSCT), patients receive high-dose MTX for CNS prophylaxis. CD22/CD19 CAR-T cells are infused 2 days after stem cell infusion. Patients with ph positive and ph-like (ABL class) B-ALL require TKIs.

Inclusion Criteria: 1. Newly diagnosed patients with Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL) or Ph-positive B-ALL in the high-risk group who have received standard induction chemotherapy; Patients with relapsed/refractory or MRD-positive B-ALL after any course of treatment without a history of immunotherapies（i.e. CD19-directed CD3 T-cell engager, inotuzumab ozogamicin, CD19 or/and CD22 CAR-T cell therapy）, who also meet any of the following criteria: (a) Ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). (b) Refuse allo-HSCT; 2. positive expression of CD19 and CD22 in peripheral blood or bone marrow primary cells detected by flow cytometry; 3. 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; 4. subjects aged 15-65 years (including 15 and 65 years), regardless of gender; 5. T-cell amplification test pass; 6. expected survival \> 3 months. Exclusion Criteria: 1. Patients who are relapsed/refractory or MRD-positive following treatment with CD19-directed CD3 T-cell engager, inotuzumab ozogamicin, CD19 or/and CD22 CAR-T cell therapy or allo-HSCT; 2. Patients with KMT2A rearrangement 3. patients with recurrence of only isolated extramedullary lesions; 4. combination of other malignant tumors; 5. previously treated with anti-CD19 or/and CD22 or/and CD3 therapies; 6. immunosuppressants use within 2 weeks prior to signing informed consent or plan to immunosuppressants after signing informed consent; 7. Presence of bacterial, fungal, viral, mycoplasmal, or other types of infection that the investigator determines to be difficult to control; 8. Patients with history of hepatitis B (HBsAg positive)or prior hepatitis B infection (defined as HBcAb positive, HBsAg negative) are eligible for enrollment provided that HBV DNA testing by PCR is negative; these subjects must undergo monthly PCR testing for HBV DNA. Patients with positive HCV antibody serology are eligible for enrollment if HCV RNA testing by PCR is negative. Positive for Treponema pallidum antibody (TP-Ab). Positive for human immunodeficiency virus (HIV) antibody. 9. History of severe immediate hypersensitivity reaction to any drug used in this study. 10. 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. 11. Pregnant or lactating women. 12. Patients with primary immunodeficiency.