CIK Cell Therapy for Relapsed or Refractory B-ALL After Early CAR-T Cell Dysfunction

Patients must have a confirmed diagnosis of refractory or relapsed B-ALL established by bone marrow aspirate and biopsy showing ≥ 20% lymphoblasts, confirmed by comprehensive flow cytometry immunotyping, MRD analysis, and G-banded karyotype. Molecular characterisation (FISH, RT-PCR, NGS) is also required.

This is the defining eligibility requirement. Patients must have received prior CAR-T cell therapy and experienced loss of CAR-T activity within 6 months of infusion — without clinical relapse at the time of enrollment. Patients whose CAR-T cells failed due to antigen escape (CD19-negative relapse) or who relapsed clinically may not meet this specific criterion.

The trial is designed for children, adolescents, and young adults (AYA) — specifically ages 1 through 39 years. Patients outside this age range are not eligible. This age restriction reflects the trial's focus on the paediatric and AYA B-ALL population for whom CAR-T therapy has the most established evidence base.

Patients must have an ECOG performance status of 0, 1, or 2. Life expectancy, as assessed by the investigator, must be at least 60 days at enrollment. Patients who are critically ill, septic, or haemodynamically unstable at the time of assessment are not eligible.

Patients must not have active sepsis, uncontrolled HIV/HBV/HCV/syphilis, disseminated intravascular coagulation (DIC), symptomatic cardiac failure, or severe respiratory failure. Serum creatinine and blood urea nitrogen must be within 1.5× the upper limit of normal. CNS leukemia with > 20 cells/μL in CSF is an exclusion.

The trial is conducted exclusively at Beijing GoBroad Hospital. International families with children or young adults meeting eligibility criteria must be able to travel to Beijing for screening, infusion, and follow-up visits. CancerFax can coordinate travel, visa, accommodation, and interpreter support.

Rather than waiting for frank relapse and restarting chemotherapy, this trial intervenes at the point of CAR-T functional loss — the specific biological event that frequently precedes relapse. CIK cells provide a mechanistically distinct anti-leukemia response that does not depend on the failing CAR-T product.

Unlike primary CAR-T therapy, CIK cell infusion does not require preparatory lymphodepletion chemotherapy — making the treatment significantly less toxic and more accessible for patients who may already have compromised marrow reserve after multiple prior lines of therapy.

CIK cells kill leukemia via NKG2D and other NK-like pathways that are not dependent on CD19 expression. This is important because many B-ALL relapses after CAR-T occur due to CD19 antigen escape. CIK cells can act against CD19-negative variants that CAR-T cells cannot target.

The mRNA-CIK arm introduces mRNA engineering — the same technology platform that underlies some of the most effective modern vaccines and emerging oncology applications — to further augment CIK cell potency and potentially improve persistence and cytotoxic function.

Beijing GoBroad Hospital has administered over 4,000 CAR-T infusions and published internationally recognised research in paediatric B-ALL, including presentations at ASH. The principal investigator, Dr. Jing Pan, is one of China's leading experts in paediatric haemato-oncology and immunotherapy.

Secondary endpoints including DOR and overall survival carry a 15-year follow-up window — providing both individual long-term monitoring and the most scientifically rigorous assessment of whether CIK therapy translates into durable paediatric survival outcomes.