Safety and Efficacy of Systemic Allogenic NK Cells in R/R Neuroblastoma

Phase 1

Recruiting

• Conditions: Neuroblastoma, Recurrent, Refractory; Neuroblastoma (NB); Neuroblastoma in Children
• Interventions: Biological: Allogenic NK cells infusion

• Registration Number: NCT06674265
• Lead Sponsor: Marzieh Ebrahimi

Brief Summary

The goal of this clinical trial is to assess safety and efficacy of systemic injection of allogenic NK cells in patients with refractory/recurrent high-risk neuroblastoma.

Is the injection of allogenic nk cells safe in patients with R/R high-risk neuroblastoma? Is the injection of allogenic nk cells effective in patients with R/R high-risk neuroblastoma? We will compare the NK cell administration group with a control group that receives conventional treatment to determine whether the intervention is safe and effective

Detailed Description

NK cells are isolated from healthy donors through the apheresis process and subsequently separated using the CLINIMACS device in a clean room environment. After quality assessment (sterility, viable cell count, purity, and phenotype of active cells), they are stored at -198°C until use. Upon need, the cells are thawed and washed, followed by checking their viability, count, and sterility. Children between the ages of 2 to 16 who meet the eligibility criteria will be added to the study. After admission, the cells are injected into the patient at a ratio of 5×10\^6 cells per kilogram of the patient's body weight. A total of 3 injections are administered to all patients. Based on the patient's response and recovery status, the need for additional injections is evaluated. If improvements in the patient's condition are observed after the last injection and confirmed by MRI MIBG, further 2 injections can continue. The intervals between injections vary based on the patient's standard treatment, and the cells are injected 10 days after the completion of each chemotherapy course.

Study Timeline

• Study First Submitted: 2024-11-03
• Study First Submitted QC: 2024-11-03
• Study First Posted: 2024-11-05
• Study Start: 2024-11-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-05
• Last Update Posted: 2025-04-09
• Primary Completion: 2026-11
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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")).

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention Group	Allogenic NK cells infusion	Patients with refractory/recurrent neuroblastoma will receive 3 to 5 systemic injections of allogeneic NK cells during the intervals between their chemotherapy courses

Primary Outcome Measures

Name	Time	Method
NK Cell Infusion Safety	After each injection to next injection and 2 weeks after last injection	The safety of the treatment is assessed using the Common Terminology Criteria for Adverse Events (CTCAE) checklist.

Secondary Outcome Measures

Name	Time	Method
Response rate comparison between control and intervention groups	6 months and 12 months	The response rate in patients in the control and treatment groups will be assessed and compared using MRI, MIBG, or PET scans.

Trial Locations

Locations (1)

Rasoul Akram Hospital; 🇮🇷 Tehran, Iran, Islamic Republic of