Clinical Trial of CD19 and CD22 CAR Sequential Therapy Versus Single CD19 CAR Bridging to HSCT for r/r B-ALL Patients

NCT ID: NCT06343090

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 353 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-12
• Study Completion Date: 2043-09-30

Brief Summary

This is a multi-center, open-label, non-randomized, two-arm, non-inferior trial. Patients with r/r B-ALL would be assigned to the CD19 CAR and CD22 CAR T-cell sequential infusion group (Sequential CAR, Arm-1) and the CD19 CAR T-cell infusion bridging to hematopoietic stem cell transplantation group (CAR+HSCT, Arm-2), according their own discretion. Patients would be also allowed to assigned to the CD19 CAR T-cell infusion without consolidation therapies group (Single CAR, additional placebo arm) according their own discretion. The primary objective is to prospectively evaluate and compare the efficacy of CD19 CAR and CD22 CAR T cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT in the treatment of r/r B-ALL. The primary endpoint is event-free survival of children and adolescent and young adult (AYA) with r/r B-ALL a treated with CD19 CAR and CD22 CAR T-cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT. A total number of 353 subjects will be enrolled.

Conditions

B-cell Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia, in Relapse; Refractory Acute Lymphoid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm-1: CD19 CAR T and CD22 CAR T-cell sequential treatments (Sequential CAR)

Group Type: EXPERIMENTAL

CD19 CAR T-cell

Intervention Type: DRUG

Murine-derived CD19 CAR T cells

CD22 CAR T cells

Intervention Type: DRUG

humanized CD22 CAR T cells

Arm-2: CD19 CAR T-cell treatment bridging to HSCT (CAR+HSCT)

Group Type: EXPERIMENTAL

CD19 CAR T-cell

Intervention Type: DRUG

Murine-derived CD19 CAR T cells

hematopoietic stem-cell transplantation

Intervention Type: PROCEDURE

allo-HSCT

Interventions

CD19 CAR T-cell

Murine-derived CD19 CAR T cells

Intervention Type: DRUG

CD22 CAR T cells

humanized CD22 CAR T cells

Intervention Type: DRUG

hematopoietic stem-cell transplantation

allo-HSCT

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Only patients who meet all the following criteria can be included in the group:

1. Patients who were diagnosed as primary refractory or relapsed B-ALL. (Criterion-reference: NCCN, version 2.2023); All the patients matched the diagnostic criteria of ALL according to the NCCN guideline (≥20% bone marrow lymphoblasts on hematopathology review of bone marrow aspirate and biopsy materials, which were confirmed by comprehensive flow cytometric immunophenotyping, minimal residual disease analysis and karyotyping of G-banded metaphase chromosomes). Molecular characterization could be obtained via interphase fluorescence in situ hybridization (FISH) testing, reverse transcriptase polymerase chain reaction (RT-PCR) testing, comprehensive testing by next-generation sequencing (NGS) for gene fusions and pathogenic mutations, etc. Determination of the World Health Organization ALL subtypes and cytogenetic and clinical risk groups were also allowed. B-ALL patients who did not achieve a complete remission after previous therapy (including the various treatment response scenarios shown in Table 1), who did not achieve a complete remission after at least two lines of TKI agents (including the various treatment response scenarios shown in Table 1), or who had ≥1 relapses were defined as having refractory or relapsed disease. Patients who were diagnosed as CD19- and CD22-positive high-risk B-ALL with continuous positive minimal residual disease (MRD) for more than three months after last therapy were also eligible. Patients had positive CD19 and CD22 expression on leukemia blasts by FCM (>80% CD19 and CD22 positive);

2. Age from 1 to 70 years old;

3. No serious allergic constitution;

4. Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) score 0 to 2;

5. Have life expectancy of at least 60 days based on investigator's judgement;

6. Voluntary informed consent is signed by self-aware patients aged 8-70 years and by legal representatives (guardians) of pediatric patients under 18 years of age.

Exclusion Criteria

• Patients with at least one of the following conditions are excluded:

1. Intracranial hypertension or unconscious;

2. Acute heart failure or severe arrhythmia;

3. Acute respiratory failure;

4. Other types of malignant tumors;

5. Diffuse intravascular coagulation;

6. Serum creatinine and/or blood urea nitrogen over 1.5 times the normal value;

7. Sepsis or other uncontrolled infection;

8. Uncontrolled diabetes mellitus;

9. Severe psychological disorder;

10. Obvious cranial lesions by cranial MRI;

11. More than 20 leukemic cells/μL in cerebrospinal fluid;

12. More than 30% leukemic cells in the peripheral blood;

13. Organ recipients;

14. Pregnant or breastfeeding;

15. Active, uncontrolled infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or treponema pallidum (TP).

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing GoBroad Hospital

OTHER

Sponsor Role: lead

The General Hospital of Western Theater Command

OTHER

Sponsor Role: collaborator

Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai

OTHER

Sponsor Role: collaborator

Shanghai Liquan Hospital

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Central People's Hospital of Zhanjiang

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Guangxi Medical University

OTHER

Sponsor Role: collaborator

Responsible Party

Jing Pan

Director of Dept of Hemato-Oncology and Immunotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing GoBroad Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tengyu Wang

Role: CONTACT

tengyu.wang@gohealtharo.com

86+18333186020

Facility Contacts

Tengyu Wang

Role: primary

tengyu.wang@gohealtharo.com

86+18333186020

Other Identifiers

BJGBYY-IIT-LCYJ-2023-003

Identifier Type: -

Identifier Source: org_study_id