This research is being done to investigate a treatment regimen of Irinotecan, Temozolomide, and Sargramostin, and an immunotherapy called Naxitamab and whether giving Naxitamab more slowly reduces the side effects for participants with relapsed or refractory neuroblastoma.
The name of the study drugs involved in this study are:
* Naxitamab (A type of monoclonal antibody) * Irinotecan (A standard of care chemotherapy) * Temozolomide (A standard of care chemotherapy) * Sargramostim (A standard of care, granulocyte-macrophage colony stimulating factor)
Histologic Diagnosis: Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines [i.e. > 2 x upper limit of normal (ULN)], at the time of initial diagnosis.
1) Any prior episode of recurrent high-risk disease following completion of frontline high-risk therapy. Patients may have received other lines of therapy for treatment of recurrent disease prior to enrolling to this trial.
2) Prior progressive high-risk disease during frontline high-risk therapy. Patients may have received other lines of therapy for treatment of progressive disease prior to enrolling to this trial.
3) Primary resistant/refractory disease (less than partial response by INRC) detected after the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, ANBL2131) that was treated with additional therapy with the goal of improving remission status prior to enrolling to this trial.
Chronic (more than 2 weeks duration) diarrhea > grade 1
Prior receipt of naxitamab
Untreated central nervous system (CNS) metastatic disease
Pregnant or currently breast feeding: Pregnant participants are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the parent with protocol therapy, participants planning to continue breastfeeding are excluded from the study.
Single group
Naxitamab
DrugRecombinant humanized anti-GD2 monoclonal antibody, single-use vial, via intravenous (into the vein) infusion per protocol.
Irinotecan
DrugTopoisomerase Inhibitor, single-dose vial, via intravenous infusion per standard of care
Temozolomide
DrugAlkylating agent, capsule, via orally (by mouth) per standard of care
Sargramostim granulocyte-macrophage colony stimulating factor
DrugRecombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF), multi-use vial, via subcutaneously (under the skin) injection per standard of care
Recommended duration of naxitamab infusion
The duration of naxitamab infusion that is safe and tolerable will be measured using the endpoint of an occurrence of any dose limiting toxicity. A modified 3+3 design will be used, where the 'modification' permits a single duration level de-escalation in addition to the typical duration group level escalation.
Frequency of severe infusion related pain as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE)
Frequency of CTCAE severe infusion related pain is defined as the count of all participants that experience a grade 3 or higher pain event as measured by CTCAE version 5.
Frequency of severe infusion related pain as measured by the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PEDS PRO-CTCAE)
Frequency of PEDS PRO-CTCAE severe infusion related pain is defined as the count of all participants that experience a score of 3 or greater on Question 1b of the PRO-CTCAE instrument.
Frequency of grade 3 or higher infusion related pain as measured by The Face, Legs, Activity, Cry, and Consolability (FLACC) Scale
Frequency of FLACC severe infusion related pain is defined as the count of all participants that experience a score of 7 or greater on the FLACC scale instrument.
Frequency of grade 3 or higher infusion related pain as measured by the Wong-Baker FACES scale
Frequency of FACES severe infusion related pain is defined as the count of all participants that experience a score of 4 or greater on the Wong-Baker FACES instrument.
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Steven DuBois, MD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Y-mAbs Therapeutics
Collaborator
