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

NCT06985498 | Not Yet Recruiting Phase 2

• 1 other identifier: SZCART03
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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. 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.

Conditions

Acute Lymphobkastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall survival

  It is measured from the date of the first course of immunotherapy to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive

  2 years

Secondary Outcomes (2)

• leukemia free survival

  2 years

• Number of adverse events

  2 years

Study Arms (1)

Sandwich strategy

EXPERIMENTAL

Combination Product: Sandwich stratergy

Interventions

Sandwich stratergy COMBINATION_PRODUCT

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.

Sandwich strategy

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• Patients with KMT2A rearrangement
• 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;
• Presence of bacterial, fungal, viral, mycoplasmal, or other types of infection that the investigator determines to be difficult to control;
• 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.
• History of severe immediate hypersensitivity reaction to any drug used in this study.
• 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.
• Pregnant or lactating women.
• Patients with primary immunodeficiency.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Central Study Contacts

Sheng-Li Xue, M.D.

CONTACT

008613328008851; slxue@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: May 22, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: March 24, 2026

Record last verified: 2026-03