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

March 6, 2026 updated by: Jing Pan, Beijing GoBroad Hospital

Pragmatic Clinical Trial of CD19 and CD22 CAR T-cell Sequential Therapy Versus Single CD19 CAR T-cell Bridging to Transplantation for Patients With Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

353

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 102206

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm-1: CD19 CAR T and CD22 CAR T-cell sequential treatments (Sequential CAR)
Drug: CD19 CAR T-cell
Murine-derived CD19 CAR T cells
Drug: CD22 CAR T cells
humanized CD22 CAR T cells
Experimental: Arm-2: CD19 CAR T-cell treatment bridging to HSCT (CAR+HSCT)
Drug: CD19 CAR T-cell
Murine-derived CD19 CAR T cells
Procedure: hematopoietic stem-cell transplantation
allo-HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EFS in CD19 CAR and CD22 CAR-T sequential infusion (Sequential CAR group) and CD19 CAR T-cell infusion bridging to HSCT (CAR+HSCT group)
Time Frame: 2-year EFS rate

Event-free survival (EFS) of children and adolescent and young adult (AYA) with r/r B-ALL treated with CD19 CAR and CD22 CAR T-cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT.

EFS is defined as the time from CD19 CAR T-cell infusion to the earliest relapse, death from any cause, or treatment failure.
2-year EFS rate

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR in Sequential CAR group and CAR+HSCT group
Time Frame: 3 months (± 1 week) ORR
Overall response rate (ORR) includes minimal residual disease-negative CR, CRh, CRi, MLFS, aplastic marrow for blood and bone marrow; central nervous system (CNS) remission; CR for lymphomatous extramedullary disease at 3 months (± 1 week) post CD19 CAR T-cell infusion in patients treated by CD19 CAR and CD22 CAR T cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT.
3 months (± 1 week) ORR
DOR in Sequential CAR group and CAR+HSCT group
Time Frame: from enrollment to the end of treatment at 15 years

Duration of remission (DOR) of children and AYA with r/r B-ALL treated by CD19 CAR and CD22 CAR T cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT.

DOR is defined as the time interval from the earliest qualifying minimal residual disease-negative response [i.e. CR, CRh, CRi, MLFS, or aplastic marrow (patients with blood and bone marrow disease), CNS remission (patients with CNS disease) and complete resolution of the lymphomatous enlargement by CT or PET-CT negative (for patients with a previous positive PET-CT) (patients with lymphomatous extramedullary disease)] to the date of relapse or death from any cause.
from enrollment to the end of treatment at 15 years
OS in Sequential CAR group and CAR+HSCT group
Time Frame: from enrollment to the end of treatment at 15 years

Overall survival (OS) of children and AYA with r/r B-ALL treated by CD19 CAR and CD22 CAR T cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT.

OS is defined as the time from CD19 CAR T-cell infusion to death from any cause.
from enrollment to the end of treatment at 15 years
Adverse events (AEs) in Sequential CAR group and CAR+HSCT group
Time Frame: from enrollment to the end of treatment at 2 years
Total number, incidence and severity of adverse events (AEs) in patients 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 AEs will be assessed according to the 2019 Consensus on Cytokine Release Syndrome and Immune-cell-associated Neurotoxicity published by the American Society of Transplantation and Cell Therapy (ASTCT), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and EBMT 2019 consensus.
from enrollment to the end of treatment at 2 years
Levels of CD19 and CD22 CAR-T cells in Sequential CAR group
Time Frame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
The levels of CD19 and CD22 CAR-T cells in peripheral blood from patients treated by CD19 CAR and CD22 CAR T cell sequential infusions will be measured by flow cytometry.
from CD19 CAR T-cell infusion to the end of treatment at 15 years
Levels of CD19 CAR-T cells in CAR+HSCT group
Time Frame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
The levels of CD19 CAR-T cells in peripheral blood from patients in CAR+HSCT group will be measured by flow cytometry.
from CD19 CAR T-cell infusion to the end of treatment at 15 years
Levels of CD19 and CD22 CAR transgene in Sequential CAR group
Time Frame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
The levels of CD19 and CD22 CAR transgene in peripheral blood from patients treated by CD19 CAR and CD22 CAR T cell sequential infusions will be measured by quantitative polymerase chain reaction (qPCR).
from CD19 CAR T-cell infusion to the end of treatment at 15 years
Levels of CD19 CAR transgene in CAR+HSCT group
Time Frame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
The levels of CD19 CAR transgene in peripheral blood from patients in CAR+HSCT group will be measured by quantitative polymerase chain reaction (qPCR).
from CD19 CAR T-cell infusion to the end of treatment at 15 years
Quantification of B cells in Sequential CAR group and CAR+HSCT group
Time Frame: from enrollment to the end of treatment at 15 years
Quantification of B cells in peripheral blood from patients treated by CD19 CAR and CD22 CAR T cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT will be measured by complete blood count and flow cytometry.
from enrollment to the end of treatment at 15 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
EFS in CD19 CAR T-cell infusion without consolidation therapies (Single CAR group)
Time Frame: 2-year EFS rate
EFS of children and adolescent and young adult (AYA) with r/r B-ALL treated with CD19 CAR T-cell infusion without consolidation therapies.
2-year EFS rate
DOR in Single CAR group
Time Frame: from enrollment to the end of treatment at 15 years
DOR of children and adolescent and young adult (AYA) with r/r B-ALL treated with CD19 CAR T-cell infusion without consolidation therapies.
from enrollment to the end of treatment at 15 years
OS in Single CAR group
Time Frame: from enrollment to the end of treatment at 15 years
OS of children and adolescent and young adult (AYA) with r/r B-ALL treated with CD19 CAR T-cell infusion without consolidation therapies.
from enrollment to the end of treatment at 15 years
ORR in Single CAR group
Time Frame: 3 months (± 1 week) ORR
ORR at 3 months (± 1 week) post CD19 CAR T-cell infusion, of children and adolescent and young adult (AYA) with r/r B-ALL treated with CD19 CAR T-cell infusion without consolidation therapies.
3 months (± 1 week) ORR
Adverse events (AEs) in Single CAR group
Time Frame: from enrollment to the end of treatment at 2 years
Total number, incidence and severity of adverse events (AEs) in patients treated by CD19 CAR T-cell infusion without consolidation therapies in the treatment of r/r B-ALL. The AEs will be assessed according to the 2019 Consensus on Cytokine Release Syndrome and Immune-cell-associated Neurotoxicity published by the American Society of Transplantation and Cell Therapy (ASTCT), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and EBMT 2019 consensus.
from enrollment to the end of treatment at 2 years
Levels of CD19 CAR-T cells in Single CAR group
Time Frame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
The levels of CD19 CAR-T cells in peripheral blood from patients treated by CD19 CAR T-cell infusion without consolidation therapies will be measured by flow cytometry.
from CD19 CAR T-cell infusion to the end of treatment at 15 years
Levels of CD19 CAR transgene in Single CAR group
Time Frame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
The levels of CD19 CAR transgene in peripheral blood from patients treated by CD19 CAR T-cell infusion without consolidation therapies will be measured by quantitative polymerase chain reaction (qPCR).
from CD19 CAR T-cell infusion to the end of treatment at 15 years
Quantification of B cells in Single CAR group
Time Frame: from enrollment to the end of treatment at 15 years
Quantification of B cells in peripheral blood from patients treated by CD19 CAR T-cell infusion without consolidation therapies will be measured by complete blood count and flow cytometry.
from enrollment to the end of treatment at 15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing GoBroad Hospital

Collaborators

Ruijin Hospital
The General Hospital of Western Theater Command
First Affiliated Hospital of Guangxi Medical University
Central People's Hospital of Zhanjiang
Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai
Shanghai Liquan Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 12, 2024

Primary Completion (Estimated)

December 1, 2042

Study Completion (Estimated)

September 30, 2043

Study Registration Dates

First Submitted

March 8, 2024

First Submitted That Met QC Criteria

March 26, 2024

First Posted (Actual)

April 2, 2024

Study Record Updates

Last Update Posted (Actual)

March 10, 2026

Last Update Submitted That Met QC Criteria

March 6, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BJGBYY-IIT-LCYJ-2023-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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