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

NCT06674265 | Recruiting Phase 1 DMC

• 1 other identifier: IR.ACECR.ROYAN.REC.1400.032
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Conditions

Neuroblastoma, Recurrent, Refractory; Neuroblastoma (NB); Neuroblastoma in Children

Keywords

Neuroblastoma; High-Risk Neuroblastoma; Natural Killer Cell; Nk Cell; adrenal gland

Outcome Measures

Primary Outcomes (1)

• NK Cell Infusion Safety

  The safety of the treatment is assessed using the Common Terminology Criteria for Adverse Events (CTCAE) checklist.

  After each injection to next injection and 2 weeks after last injection

Secondary Outcomes (1)

• Response rate comparison between control and intervention groups

  6 months and 12 months

Study Arms (2)

Intervention Group

ACTIVE COMPARATOR

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

Biological: Allogenic NK cells infusion

Control Group

NO INTERVENTION

Patients in the control group will receive no cells and just conventional treatments will be administered to them.

Interventions

Allogenic NK cells infusion BIOLOGICAL

Natural Killer (NK) cells are extracted from a healthy donor through apheresis and processed in a clean room using the CLINIMACS device. After quality assessment, these cells are stored at -198°C until needed. When required, the cells are thawed, washed, and evaluated for viability and sterility before being administered to the patient at a dosage of 5 × 10\^6 cells per kilogram of body weight. Two further injections may be considered based on the patient's response and confirmed improvement via MRI MIBG. Injections are scheduled seven to ten days after each chemotherapy course according to the standard treatment protocol.

Intervention Group

Eligibility Criteria

• Age: 2 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• Evidence of relapse or progression of neuroblastoma after autologous peripheral blood stem cell transplantation or aggressive therapy.
• A minimum life expectancy of 6 months.
• Patients must have a pathological diagnosis of neuroblastoma and/or confirmation of tumor cells in the bone marrow with increased urinary catecholamines.
• 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")).

You may not qualify if:

• 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.
• 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).
• 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.
• 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.
• Insufficient cardiovascular function Shortening fraction \< 27% by ECHO OR Ejection fraction \< 50% by ECHO or gated radionuclide study.
• 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.
• 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).
• Receiving 0.5 mg/kg/day of systemic steroids (equivalent to prednisone) for at least 7 days before enrollment.
• Receiving CYP3A4 inducers or inhibitors at least 7 days before study enrollment.
• 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).
• 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.

Sponsors & Collaborators

• Marzieh Ebrahimi: lead
• Royan Institute: collaborator
• Iran University of Medical Sciences: collaborator

Study Sites (1)

Rasoul Akram Hospital

Tehran, 1445613131, Iran

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Recurrence

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dr. Marzieh Ebrahimi, PhD. in Medical Immunology

  Royan Institute

  STUDY CHAIR

• Dr. Mohammad Faranoush, Pediatric Oncologist

  Iran University of Medical Science

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. Marzieh Ebrahimi

CONTACT

+98 9123448359; m.ebrahimi@royan-rc.ac.ir

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medical Immunology

Study Record Dates

• First Submitted: November 3, 2024
• First Posted: November 5, 2024
• Study Start: November 10, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)