This is a phase II study looking at patient response to treatment with the combination dinutuximab, temozolomide, irinotecan, and GM-CSF.
Patients must be ≥ 1 year and ≤31 years of age at the time of enrollment on the study.
Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
Patients must have high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients whose disease was initially considered low or intermediate risk but then reclassified as high-risk neuroblastoma prior to enrollment also meet this criteria.
SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for discrete lymph nodes ≥ 15mm on short axis. Lesions meeting size criteria will be considered measurable.
Patients who are pregnant, breast feeding, or unwilling to use effective contraception during the study
Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
Patients with disease of any major organ system that would compromise their ability to withstand therapy.
Patients with > Grade 2 diarrhea.
Single group
Universal Donor (UD) TGFβi NK Cells
DrugPatients will receive a dose of 1x108 UD TGFβi NK cells/kg per treatment cycle on day 8 of each cycle
Temozolomide
DrugEnteral or IV daily on days 1-5 of each cycle For patients ≥ 0.5 m2: 100 mg/m2/dose For patients \< 0.5 m2: 3.3 mg/kg/dose MAXIMUM dose = 200 mg
Irinotecan
Drug50mg/m2/dose IV daily on days 1-5 of each cycle
Dinutuximab
Drug17.5mg/m2/dose IV daily on days 2-5 of each cycle
GM-CSF
Drug250mcg/m2/dose subcutaneous (preferred) or IV daily on days 6-12 of each cycle
Best Overall Response Rate of Evaluable Patients
The response evaluation is based on central review or site review (when central review is not available) of patient diagnostic assessments. Response is determined by the NANT response criteria v2.0 (https://doi.org/10.1002/pbc.26940). 1. Complete response 2. Partial response 3. Minor response 4. Stable response 5. Progressive disease 6. Early death from malignant disease 7. Early death from toxicity Evaluable response patients have received sufficient therapy (1) and have sufficient response evaluation data to assess best overall response (2) including patients in categories f and g 1. is defined as at least 75% of all therapeutic agents in course 1, or less than 75% in course 1 due to clinical signs of tumor progression or therapy related toxicity. 2. is defined as presence of a disease evaluation for each of the 3 disease parameters (bone, soft tissue, bone marrow) at one or more timepoints after enrollment. Best Overall Response Rate = (a+b+c)/ (a+b+c+d+e+f+g).
Proportion of Evaluable Participants with Grade 3 or Greater Hematologic Toxicities or Any Hematologic Toxicities Attributed to this therapy.
Describe the toxicity profiles for grade 3 or greater hematologic toxicities associated with the protocol therapy any hematologic toxicities attributed to NK cells. All patients who start treatment for this protocol are evaluable for toxicity reporting.
Proportion of Evaluable of Participants with Grade 2 or Greater Non-Hematologic Toxicities or Any Non-Hematologic Toxicities Attributed to this therapy.
Describe the toxicity profiles for grade 2 or greater non-hematologic toxicities associated with the protocol therapy any non-hematologic toxicities attributed to NK cells. All patients who start treatment for this protocol are evaluable for toxicity reporting
Click on the lead sponsor to view all of their trials.
New Approaches to Neuroblastoma Therapy Consortium
Lead sponsor
Nationwide Children's Hospital
Collaborator
United Therapeutics
Collaborator
Children's Neuroblastoma Cancer Fund
Collaborator
