CIK Cell Therapy for Relapsed or Refractory Acute B-Lymphoblastic Leukemia: Prognostic Impact on Patients With Early CAR-T Cell Dysfunction

Cytokine-induced Killer(CIK) Cell Therapy and Its Impact on Early Functional Exhaustion of Chimeric Antigen Receptor-T(CAR-T) Cells in Relapsed or Refractory Acute B-Lymphoblastic Leukemia: A Prospective Study

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, in Relapse; B-cell Acute Lymphoblastic Leukemia; Refractory Acute Lymphoid Leukemia
• Intervention / Treatment: Drug: peripheral blood lymphocytes; Drug: CIK cell

• Study Type: Interventional
• Enrollment (Estimated): 213
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tengyu Wang; Phone Number: 86+18333186020; Email: tengyu.wang@gohealtharo.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 102206
      • Recruiting
      • Beijing GoBroad Hospital
      • Contact: Tengyu Wang; Phone Number: 86+18333186020; Email: tengyu.wang@gohealtharo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: peripheral blood lymphocytes	Drug: peripheral blood lymphocytes; autologous or allogeneic peripheral blood lymphocytes
Experimental: CIK cells	Drug: CIK cell; autologous or allogeneic cytokine-induced killer (CIK) cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2-year EFS rate

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2-year EFS rate
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	2-year PFS rate
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.	from enrollment to the end of treatment at 15 years
Overall survival(OS) in CIK infusion group	OS is defined as the time from CIK-cell infusion to death from any cause.	from enrollment to the end of treatment at 15 years

Collaborators and Investigators

• Sponsor: Beijing GoBroad Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2024
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Leukemia, Lymphoid; Leukemia; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma
• Other Study ID Numbers: BJGBYY-IIT-LCYJ-2024-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No