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

Launched by BEIJING GOBROAD HOSPITAL · Mar 26, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating two different treatments for children and young adults with a type of leukemia called B-cell Acute Lymphoblastic Leukemia (B-ALL) that has come back or has not responded to previous treatments. The trial compares the effectiveness of giving two types of special immune cells (called CAR T-cells) sequentially—first targeting CD19 and then CD22—against using just the CD19 CAR T-cells followed by a procedure to replace blood-forming cells (called hematopoietic stem cell transplantation, or HSCT). The goal is to see which approach helps patients live longer without their leukemia returning.

To be eligible for this trial, patients should be between 1 and 39 years old and have been diagnosed with treatment-resistant or relapsed B-ALL. They must also have certain markers on their leukemia cells (CD19 and CD22) and cannot have any serious health conditions that could complicate treatment. If enrolled, participants can expect to receive either treatment based on their choice and will be monitored closely for how well the treatments work. It's important to note that the study is currently recruiting participants, and those interested should discuss it with their healthcare provider.

Gender

ALL

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).