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.
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.
Loss of CAR-T cell activity within 6 months after previous CAR-T therapy and no relapse.
Age between 1 and 39 years old.
No severe allergic constitution.
Received bendamustine treatment within the past 9 months;
Intracranial hypertension or impaired consciousness in the brain;
Symptomatic heart failure or severe arrhythmia;
Symptoms of severe respiratory failure;
Parallel
peripheral blood lymphocytes
Drugautologous or allogeneic peripheral blood lymphocytes
CIK cell
Drugautologous or allogeneic cytokine-induced killer (CIK) cells
Event-free survival(EFS) in CIK infusion group
EFS is defined as the time from CIK-cell infusion to the earliest relapse, death from any cause, or treatment failure
Progression-free survival(PFS) in CIK infusion group
PFS is defined as the time from CIK-cell infusion until objective tumor progression or death depending on study protocol
Duration of response(DOR) in CIK infusion group
DOR is defined as the time interval from the earliest qualifying minimal residual disease-negative response \[i.e. complete remission(CR),complete remission with partial hematological recovery(CRh), complete remission with incomplete hematological recovery(CRi), morphologic leukemia-free state(MLFS), or aplastic marrow (patients with blood and bone marrow disease), central nervous system(CNS) remission (patients with CNS disease) and complete resolution of the lymphomatous enlargement by CT or positron emission tomography(PET)-CT negative (for patients with a previous positive PET-CT) (patients with lymphomatous extramedullary disease)\] to the date of relapse or death from any cause.
Overall survival(OS) in CIK infusion group
OS is defined as the time from CIK-cell infusion to death from any cause.
EFS in mRNA-CIK infusion group
EFS is defined as the time from mRNA-CIK-cell infusion to the earliest relapse, death from any cause, or treatment failure
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