Overview

This is a single-center, double-blind, randomized trial. Patients with relapsed or refractory acute B-lymphoblastic leukemia(r/r B-ALL) experiencing early functional exhaustion of CAR-T cells will be randomly allocated into three groups: the control cell group, the CIK treatment group, and the messenger RNA(mRNA)-CIK treatment group. The primary objective of the study is to evaluate the prognostic impact of CIK cell therapy on the early functional exhaustion of CAR-T cells in children and adolescent and young adult (AYA) with r/r B-ALL. The primary endpoint of the study is the event-free survival rate of these patient in the CIK cell therapy group.A total number of 213 subjects will be enrolled.

Eligibility

Inclusion Criteria:

• A patient must meet all of the following to be enrolled:
  1. A confirmed diagnosis of refractory or relapsed B-ALL (criteria reference: NCCN, 2024.4), where all patients meet the National Comprehensive Cancer Network(NCCN) guidelines for the diagnosis of acute lymphoblastic leukemia (hematopathological examination of bone marrow aspirate and biopsy tissue showing ≥20% lymphoblasts in the bone marrow, confirmed by comprehensive flow cytometry (FCM) immunotyping, minimal residual disease analysis, and G-banded metaphase chromosome karyotype analysis). Molecular characteristics can be described through methods such as interphase fluorescence in situ hybridization (FISH) testing, reverse transcription polymerase chain reaction (RT-PCR) testing, and next-generation sequencing (NGS) for comprehensive detection of fusion genes and pathogenic mutations. Determination can also be made by the World Health Organization's subtypes of acute lymphoblastic leukemia, as well as cytogenetic and clinical risk groups.
  2. Loss of CAR-T cell activity within 6 months after previous CAR-T therapy and no relapse.
  3. Age between 1 and 39 years old.
  4. No severe allergic constitution.
  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
  6. Life expectancy, as judged by the investigator, of at least 60 days.
  7. Patients with self-awareness between 8 and 39 years of age voluntarily sign an informed consent, and the legal representative (guardians) of child patients under 18 years of age voluntarily signs an informed consent.

Exclusion Criteria:

• A patient with at least one of the following conditions will be excluded:
  1. Received bendamustine treatment within the past 9 months;
  2. Intracranial hypertension or impaired consciousness in the brain;
  3. Symptomatic heart failure or severe arrhythmia;
  4. Symptoms of severe respiratory failure;
  5. With other types of malignant tumors;
  6. Disseminated intravascular coagulation;
  7. Serum creatinine and/or blood urea nitrogen ≥ 1.5 times the normal value;
  8. Suffering from sepsis or other uncontrollable infections;
  9. Uncontrollable diabetes;
  10. Severe mental disorders;
  11. Significant lesions in the brain as detected by head magnetic resonance imaging;
  12. Leukemic cells in the cerebrospinal fluid \>20 cells/μL;
  13. Peripheral blood leukemic cell proportion \>30%;
  14. Have undergone organ transplantation;
  15. Female patients (those with childbearing potential) are pregnant or lactating;
  16. Active or uncontrollable infectious diseases, such as hepatitis (HBV, HCV), HIV, or syphilis.