Using NK cells to treat high-risk neuroblastoma in children

Evaluation of Safety and Efficacy Evaluation Post Intravenous Infusion of Activated NK Cells in Recurrent and Refractory High-risk Neuroblastoma Patients

This study is testing if injections of special immune cells can help children aged 2 to 16 with tough-to-treat neuroblastoma feel better and improve their chances of recovery.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 2 Years to 16 Years
• Sex: All
• Sponsor: Kian Immune Cell Company (industry)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Tehran)
• Trial ID: NCT06674265 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of systemic injections of allogenic natural killer (NK) cells in children aged 2 to 16 with refractory or recurrent high-risk neuroblastoma. The NK cells are sourced from healthy donors and undergo rigorous quality assessments before being administered to patients. Participants will receive a total of three injections, with the possibility of additional doses based on their response to treatment, and their progress will be monitored through imaging techniques. The study compares outcomes between those receiving NK cell therapy and a control group receiving standard treatments.

Who should consider this trial

Good fit: Ideal candidates are children aged 2 to 16 with high-risk neuroblastoma that is resistant to standard treatments.

Not a fit: Patients with insufficient bone marrow or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children with high-risk neuroblastoma who have not responded to conventional therapies.

How similar studies have performed: While the use of NK cells in cancer treatment is an emerging field, this specific approach in high-risk neuroblastoma is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. High-risk neuroblastoma that is resistant to standard induction therapy based on COG (Children's Oncology Group) criteria (according to INRG criteria and having received at least 4 cycles of multi-drug induction chemotherapy, and not responding to conventional treatments).
2. Evidence of relapse or progression of neuroblastoma after autologous peripheral blood stem cell transplantation or aggressive therapy.
3. A minimum life expectancy of 6 months.
4. Patients must have a pathological diagnosis of neuroblastoma and/or confirmation of tumor cells in the bone marrow with increased urinary catecholamines.
5. Measurable residual disease based on imaging findings using Curie scoring or MIBG or PET imaging criteria (1: measurable tumor of at least 10 mm in one dimension on MRI or CT scan with positive uptake on I-123 MIBG scan ("MIBG avid") oOR 2): increased FDG uptake on 18F-FDG PET-CT or PET-MRI ("PET avid")).

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Exclusion Criteria:

1. Insufficient bone marrow function: Platelet count \> 50,000/µL, independent of transfusion (no platelet transfusion within one week). Absolute neutrophil count (ANC) maximum of 500 per microliter. Hemoglobin \> 10 grams per deciliter.
2. Insufficient liver function: Plasma bilirubin level more than 1.5 times the upper limit of normal (ULN). SGPT (ALT) at least three times the upper limit of normal (a level of 45 units per liter is considered the upper limit of normal).
3. Insufficient kidney function: Creatinine clearance or estimated radioisotope GFR \< 70 ml/min/1.73m². Plasma creatinine level more than 1.5 times the upper limit of normal based on age/gender.
4. Insufficient central nervous system function if seizures are present, entry into the study is not possible and if seizures are not well controlled with anticonvulsant drugs.

3- Insufficient cardiovascular function Shortening fraction \< 27% by ECHO OR Ejection fraction \< 50% by ECHO or gated radionuclide study.

4- Insufficient pulmonary function evidence of dyspnea at rest. Exercise intolerance. Chronic need for oxygen and room air pulse oximetry \< 94% if pulse oximetry evaluation is clinically indicated. Presence of current pleural or pericardial effusion.

5- Inability to tolerate new treatment due to emergency conditions. 6- Elevated catecholamines (more than twice the ULN) or sole involvement of bone marrow (bone marrow positive for NB as the only evaluable disease without confirmatory pathology report).

7- Receiving 0.5 mg/kg/day of systemic steroids (equivalent to prednisone) for at least 7 days before enrollment.

8- Receiving CYP3A4 inducers or inhibitors at least 7 days before study enrollment.

9- Diagnosis of any other malignancy alongside the diagnosis of neuroblastoma. 10- Diarrhea \> Grade 2 (4 to 6 stools per day). 11- Significant illness not covered by exclusion criteria but interfering with the study process or increasing the intensity of treatment with NK cells.

12- Participation in another clinical trial. 13- Severe impairment of major organ functions, such as renal, cardiac, hepatic, neurological, pulmonary, or gastrointestinal toxicity above Grade 2 according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTC v5.0).

14- Inability to comply with protocol requirements. 15- Lack of confirmed and signed consent by the patient's guardians. 16- Evidence of HIV disease (Human Immunodeficiency Virus) or positive serology for HIV.

Where this trial is running

Tehran

• Rasoul Akram Hospital — Tehran, Iran (RECRUITING)

Study contacts

• Principal investigator: Dr. Mohammad Faranoush, Pediatric Oncologist — Iran University of Medical Science
• Study coordinator: Dr. Marzieh Ebrahimi

Conditions: Neuroblastoma, Recurrent, Refractory, Neuroblastoma, Neuroblastoma in Children, High-Risk Neuroblastoma, Natural Killer Cell, Nk Cell, adrenal gland