Clinical trial NCT06343090: Clinical Trial of CD19 and CD22 CAR Sequential Therapy Versus Single CD19 CAR Bridging to HSCT for r/r B-ALL Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: B-cell Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia, in Relapse
Refractory Acute Lymphoid Leukemia
Lead sponsor: Beijing GoBroad Hospital
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 353
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: a prospective cohort study
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: 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)
timeFrame: 2-year EFS rate
Secondary outcomes:
measure: ORR in Sequential CAR group and CAR+HSCT group
timeFrame: 3 months (± 1 week) ORR
measure: DOR in Sequential CAR group and CAR+HSCT group
timeFrame: from enrollment to the end of treatment at 15 years
measure: OS in Sequential CAR group and CAR+HSCT group
timeFrame: from enrollment to the end of treatment at 15 years
measure: Adverse events (AEs) in Sequential CAR group and CAR+HSCT group
timeFrame: from enrollment to the end of treatment at 2 years
measure: Levels of CD19 and CD22 CAR-T cells in Sequential CAR group
timeFrame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
measure: Levels of CD19 CAR-T cells in CAR+HSCT group
timeFrame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
measure: Levels of CD19 and CD22 CAR transgene in Sequential CAR group
timeFrame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
measure: Levels of CD19 CAR transgene in CAR+HSCT group
timeFrame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
measure: Quantification of B cells in Sequential CAR group and CAR+HSCT group
timeFrame: from enrollment to the end of treatment at 15 years
Other outcomes:
measure: EFS in CD19 CAR T-cell infusion without consolidation therapies (Single CAR group)
timeFrame: 2-year EFS rate
measure: DOR in Single CAR group
timeFrame: from enrollment to the end of treatment at 15 years
measure: OS in Single CAR group
timeFrame: from enrollment to the end of treatment at 15 years
measure: ORR in Single CAR group
timeFrame: 3 months (± 1 week) ORR
measure: Adverse events (AEs) in Single CAR group
timeFrame: from enrollment to the end of treatment at 2 years
measure: Levels of CD19 CAR-T cells in Single CAR group
timeFrame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
measure: Levels of CD19 CAR transgene in Single CAR group
timeFrame: from CD19 CAR T-cell infusion to the end of treatment at 15 years
measure: Quantification of B cells in Single CAR group
timeFrame: from enrollment to the end of treatment at 15 years
Locations:
city: Beijing
country: China
facility: Beijing GoBroad Hospital
state: Beijing
Study officials:
References: