Haploidentical Donor Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) for Relapsed & Refractory Neuroblastoma

The goal of this study is to demonstrate that cytokine-induced memory-like natural killer cells (CIML-NK cells) can be generated from donor cells and infused safely into patients with relapsed or refractory neuroblastoma during dinutuximab-based therapy.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma
• Intervention / Treatment: Biological: CIML-NK Cells

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Caitlin Cottrell, BSN, RN; Phone Number: 513-803-7039; Email: Caitlin.cottrell@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Caitlin Cottrell; Phone Number: 513-803-7039; Email: Caitlin.cottrell@cchmc.org
      • Principal Investigator: Christopher Dandoy, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 1-39 years at the time of study enrollment
• With diagnosis of neuroblastoma with histologic verification
• Classified as high-risk neuroblastoma as defined by Children's Oncology Group (COG) risk classification, including patients initially classified as low or intermediate risk at diagnosis with subsequent reclassification as high-risk disease

• With relapsed or refractory disease, including at least one of the following:

  1. Recurrent disease at any time after completion of frontline therapy
  2. Progressive disease at any time following standard induction therapy
  3. Primary resistant or refractory disease defined by failure to achieve a complete response by International Neuroblastoma Response Criteria (INRC) after at least four cycles of standard, multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol

• Patients must have evaluable disease documented within four weeks of study enrollment. Evaluable disease must include at least one of the following:

  1. Measurable tumor (>10 mm in at least one dimension) on MRI or CT scan that is either MIBG, FDG or 68Ga-DOTATATE avid
  2. One or more MIBG, FDG, or 68Ga-DOTATATE avid bone lesion
  3. Microscopic marrow metastasis based on routine morphology and/or immunohistochemistry in at least one sample from bilateral aspirates and biopsies at the time of study enrollment.
• With performance level of >50% on Lansky (<16 years) or Karnofsky (>16 years) scales. Patients who are wheelchair bound due to paralysis will be considered ambulatory when assessing their performance score.
• Adequate baseline cardiac and pulmonary function including a left ventricular ejection fraction (LVEF) >50% by echocardiogram and pulse oximetry >92% on room air documented within four weeks of study enrollment.
• Adequate baseline hematologic function: peripheral absolute neutrophil count (ANC) ≥500/µL, with no receipt of long-acting myeloid growth factors within 14 days or short-acting myeloid growth factors within 7 days of study entry, and a platelet count ≥50,000/µL, with patients required to be transfusion independent for at least 7 days, unless cytopenias are related to marrow metastasis as defined above.
• With available haploidentical related donors.

Exclusion Criteria:

• Infectious disease: Active, uncontrolled infection or received a live vaccine within 30 days prior to study enrollment.
• Cardiac function: LVEF <50% by echocardiogram, serious uncontrolled cardiac arrhythmias, or history of myocarditis or congestive heart failure (New York Heart Association Functional Classification III or IV)
• Pulmonary function: Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring systemic corticosteroid treatment.
• Renal function: Glomerular Function Rate (GFR) <50 mL/min/1.73 m2 as measured by cystatin C or NM GFR
• Hepatic function: Total bilirubin >5 mg/dL, AST and ALT >10 times the upper limit of normal
• Concomitant medications: receiving >0.5 mg/kg prednisone equivalent daily
• Receipt of any concomitant investigational treatments within 30 days at the time of the infusion of the IP. These investigational treatments include drugs, biologics, or devices that are still under investigation in clinical trials or research settings. The use of such agents may confound study results or pose additional safety risks
• Known allergy or hypersensitivity reaction to IL-2 injections
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cytokine-Induced Memory-Like Natural Killer (CIML-NK) Cells; The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product.

Biological: CIML-NK Cells; The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product. At the time of infusion, the product is comprised of: Cytokine-Induced Memory-Like NK cells (CIML-NK cells); Human Serum Albumin; Plasmalyte The concentration and total cell number of CIML-NK cells in the product will vary based on the recipient body weight and the dose requested.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infusional Toxicity	Number of subjects who receive an infusion of cytokine-induced memory-like natural killer cells (CIML-NK cells) without grade 3-4 infusional toxicity events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 divided by the number of patients enrolled.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response or Disease Stability to Study Treatment	Number of subjects who demonstrate clinical response to study treatment assessed by modified International Neuroblastoma Response Criteria.	end of cycle 2 (approximately study day 56)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence of Cytokine-induced Memory-like Natural Killer (CIML-NK) cells in the Recipient's Peripheral Blood	Number of subjects who have persistence of CIML-NK cells in the recipient's peripheral blood, assessed via short tandem repeats assays	14 days

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Christopher Dandoy, MD, MS, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma
• Other Study ID Numbers: 2025-0656

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No