CIK cell therapy for relapsed or refractory B‑cell acute lymphoblastic leukemia with early CAR‑T 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

We are testing whether giving regular or mRNA‑modified CIK cells helps children and young adults with relapsed or refractory B‑cell ALL who show early CAR‑T cell exhaustion stay free of relapse or disease progression longer.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 213 (estimated)
• Ages: 1 Year to 39 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06389305 on ClinicalTrials.gov

What this trial studies

This is a single‑center, double‑blind, randomized trial enrolling children and adolescent/young adult patients with relapsed or refractory B‑ALL who show early functional exhaustion of prior CAR‑T cells. Eligible participants will be randomly assigned to one of three arms: a control cell group, a CIK cell treatment group, or an mRNA‑modified CIK treatment group. The trial tests the prognostic impact of CIK therapy on early CAR‑T dysfunction, with the primary endpoint being event‑free survival in the CIK treatment arm. A total of 213 subjects will be treated at Beijing GoBroad Hospital using peripheral blood‑derived lymphocyte infusions including CIK and mRNA‑CIK products.

Who should consider this trial

Good fit: Children, adolescents, and young adults with relapsed or refractory B‑cell ALL who meet NCCN diagnostic criteria and demonstrate early functional exhaustion of CAR‑T cells are the intended participants.

Not a fit: Patients without CAR‑T cell exhaustion, with other leukemia subtypes, who fail to meet the inclusion criteria, or who cannot receive treatment at the Beijing site are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could prolong event‑free survival and reduce relapses in children and young adults with r/r B‑ALL who experience early CAR‑T failure.

How similar studies have performed: CIK cell therapy has shown anti‑leukemia activity in small studies, but using CIK to rescue early CAR‑T dysfunction and the mRNA‑CIK approach are relatively novel and not yet well proven.

Eligibility criteria

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.

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