Comparing CD19 and CD22 CAR T-cell therapies for treating relapsed B-ALL

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 study is testing whether giving patients with relapsed B-cell Acute Lymphoblastic Leukemia two different types of CAR T-cell therapies one after the other works better than just one type followed by a stem cell transplant.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 353 (estimated)
• Ages: 1 Year to 70 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (Academic / other)
• Drugs / interventions: CAR T
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06343090 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of sequential infusions of CD19 and CD22 CAR T-cells compared to CD19 CAR T-cell infusion followed by hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL). It is a multi-center, open-label, non-randomized trial where patients can choose their treatment arm. The primary goal is to assess event-free survival in children and young adults receiving these therapies. A total of 353 subjects will be enrolled to provide robust data on treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are children and young adults diagnosed with primary refractory or relapsed B-ALL.

Not a fit: Patients with non-B-ALL or those who do not meet the specific diagnostic criteria for B-ALL may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could offer a more effective treatment option for patients with relapsed or refractory B-ALL.

How similar studies have performed: Other studies have shown promise with CAR T-cell therapies, but this specific sequential approach is relatively novel.

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).

Where this trial is running

Beijing, Beijing Municipality

• Beijing GoBroad Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Tengyu Wang

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