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

NCT06343090 | Recruiting DMC

• 1 other identifier: BJGBYY-IIT-LCYJ-2023-003
• Study Type: interventional
• Target: 353
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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)

  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 Outcomes (9)

• ORR in Sequential CAR group and CAR+HSCT group

  3 months (± 1 week) ORR

• DOR in Sequential CAR group and CAR+HSCT group

  from enrollment to the end of treatment at 15 years

• OS in Sequential CAR group and CAR+HSCT group

  from enrollment to the end of treatment at 15 years

• Adverse events (AEs) in Sequential CAR group and CAR+HSCT group

  from enrollment to the end of treatment at 2 years

• Levels of CD19 and CD22 CAR-T cells in Sequential CAR group

  from CD19 CAR T-cell infusion to the end of treatment at 15 years

Other Outcomes (8)

• EFS in CD19 CAR T-cell infusion without consolidation therapies (Single CAR group)

  2-year EFS rate

• DOR in Single CAR group

  from enrollment to the end of treatment at 15 years

• OS in Single CAR group

  from enrollment to the end of treatment at 15 years

Study Arms (2)

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

EXPERIMENTAL

Drug: CD19 CAR T-cell; Drug: CD22 CAR T cells

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

EXPERIMENTAL

Drug: CD19 CAR T-cell; Procedure: hematopoietic stem-cell transplantation

Interventions

CD19 CAR T-cell DRUG

Murine-derived CD19 CAR T cells

Arm-1: CD19 CAR T and CD22 CAR T-cell sequential treatments (Sequential CAR); Arm-2: CD19 CAR T-cell treatment bridging to HSCT (CAR+HSCT)

CD22 CAR T cells DRUG

humanized CD22 CAR T cells

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

hematopoietic stem-cell transplantation PROCEDURE

allo-HSCT

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

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Only patients who meet all the following criteria can be included in the group:
• 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);
• Age from 1 to 70 years old;
• No serious allergic constitution;
• Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) score 0 to 2;
• Have life expectancy of at least 60 days based on investigator's judgement;
• 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.

You may not qualify if:

• Patients with at least one of the following conditions are excluded:
• Intracranial hypertension or unconscious;
• Acute heart failure or severe arrhythmia;
• Acute respiratory failure;
• Other types of malignant tumors;
• Diffuse intravascular coagulation;
• Serum creatinine and/or blood urea nitrogen over 1.5 times the normal value;
• Sepsis or other uncontrolled infection;
• Uncontrolled diabetes mellitus;
• Severe psychological disorder;
• Obvious cranial lesions by cranial MRI;
• More than 20 leukemic cells/μL in cerebrospinal fluid;
• More than 30% leukemic cells in the peripheral blood;
• Organ recipients;
• Pregnant or breastfeeding;

Sponsors & Collaborators

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

Study Sites (1)

Beijing GoBroad Hospital

Beijing, Beijing Municipality, 102206, China

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Central Study Contacts

Tengyu Wang

CONTACT

86+18333186020; tengyu.wang@gohealtharo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Dept of Hemato-Oncology and Immunotherapy

Model Details: a prospective cohort study

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: April 2, 2024
• Study Start: April 12, 2024
• Primary Completion (Estimated): December 1, 2042
• Study Completion (Estimated): September 30, 2043
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)