NCT02573896

Immunotherapy of Relapsed Refractory Neuroblastoma With Expanded NK Cells

A Phase I Dose Escalation Study of Autologous Expanded Natural Killer (NK) Cells for Immunotherapy of Relapsed Refractory Neuroblastoma With Dinutuximab +/- Lenalidomide

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: New Approaches to Neuroblastoma Therapy Consortium · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Not accepted

Summary

This NANT trial will determine the maximum tolerated dose (MTD) of autologous expanded natural killer (NK) cells when combined with standard dosing of dinutuximab and will assess the feasibility of adding lenalidomide at the recommended Phase II dose of the expanded NK cells with dinutuximab, for treatment of children with refractory or recurrent neuroblastoma.

Detailed description

This NANT trial will determine the maximum tolerated dose (MTD) of autologous expanded natural killer (NK) cells when combined with standard dosing of dinutuximab and will assess the feasibility of adding lenalidomide at the recommended Phase II dose of the expanded NK cells with dinutuximab, for treatment of children with refractory or recurrent neuroblastoma. Dinutuximab is a chimeric antibody against GD2, which is expressed on a majority of neuroblastoma cells. It has been shown to increase EFS and OS in patients with high-risk neuroblastoma when given after autologous stem cell transplant in combination with subcutaneous GM-CSF and intravenous IL-2, followed by isotretinoin. Lenalidomide has been studied in children with solid tumors and can safely be given to patients based on 2 prior trials in children. It was also shown to have immunomodulatory effects and is synergistic with dinutuximab. Lenalidomide is also an oral agent that can be given in the outpatient setting. Natural killer cells are lymphocytes of the innate immune system that have the ability to recognize and kill malignant cells, including neuroblastoma. Dinutuximab and lenalidomide both exert part of their anti-cancer effect through the activation of natural killer cells. Patients were given these in combination in the NANT 2011-04 study where the safety and immunomodulatory effect were established. The dose level proposed in this study is based off of these data. Natural killer cells are dysfunctional and low in number in many cancer patients, and number and function are further suppressed by chemotherapy and radiation. Investigators hypothesize that autologous NK cells can be expanded and activated ex vivo and readministered to restore number and function, and in combination with lenalidomide and dinutuximab will provide an anti-tumor effect in patients with relapsed or refractory neuroblastoma. Investigators will determine the feasibility of centralized expansion, cryopreservation, and distribution of autologous NK cells. Investigators will then determine the maximum tolerated dose by assessing the toxicities of autologous expanded NK cells given with dinutuximab; by assessing the toxicities, cytokinetics and immunomodulatory effects, Investigators will select the recommended Phase II dose of the two-agent combination after dose escalation of the NK cells and then adding lenalidomide to the combination to establish the three-agent combination. Cytokinetics (persistence of infused NK cells) and immune function studies will be required for all patients entered on this study. In addition to routine assessment of response, quantification of rare tumor cell detection in blood and bone marrow using TLDA will also provide another measure of possible anti-tumor efficacy to support the rationale for the final schedule chosen.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	Dinutuximab	17.5 mg/m2/day of dinutuximab will be given for 4 consecutive days (days 1-4 of each course) via intravenous infusion over ten hours.
BIOLOGICAL	NK Cells	The designated dose of NK Cells will be infused on Day 5 by IV drip using a Y infusion set with a filter-less chamber. Cells should not be delivered at a rate faster than 10 ml/kg/hr (as determined by drip rate or syringe push rate), and should not take longer than one hour for total infusion time if possible.
DRUG	Lenalidomide	25 mg/m2/day of Lenalidomide will be given at Dose Level 4, once daily with or without food by mouth on days -6 through +14.

Timeline

• Start date: 2019-01-14
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2015-10-12
• Last updated: 2026-03-23

Locations

11 sites across 1 country: United States

Regulatory

• FDA-regulated drug study