Health TrialsbyHealthPanel

NK Cells Infusions With Irinotecan, Temozolomide, and Dinutuximab

ConditionsRelapsed NeuroblastomaRefractory Neuroblastoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
AgeUp to 29
SponsorNationwide Children's Hospital

About this trial

This is a Phase 1 study with Phase 2 expansion cohort. Phase 1 will assess the safety and tolerability of universal donor TGFβi NK Cell in combination with irinotecan, temozolomide, and dinituximab. The phase 2 of the study will estimate the response to treatment.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Less than 30 years of age when registered on the study.

Patients must have a histologic verification of neuroblastoma (NBL) or ganglioneuroblastoma or NBL cells in bone marrow with or without elevated urine catecholamines.

Recurrent disease; or

First episode of progressive disease (new lesion, increase in size, previous negative bone marrow) during initial multi-drug, induction myelosuppressive therapy; or

Disqualifiers

Patients who are pregnant or breastfeeding

Patients with elevated catecholamines (>2x ULN) only.

Patients must not have received 0.5 mg/ kg/ day (prednisone equivalent) doses of systemic steroids for at least 7 days prior to enrollment.

Patients must not have received CYP3A4 inducer or inhibitor for at least 7 days prior to study enrollment.

Trial design

Design model

Single group

Treatments tested in this trial

  • Natural Killer Cells

    Biological/Vaccine

    NK cells dose 1x 108 cells/ kg on day 8 of each cycle

  • Temozolomide

    Drug

    Temozolomide 100mg/m2/dose PO or IV daily on Days 1-5; if given orally, must be at least one hour prior to Irinotecan. For patients whose body surface area is \<0.5m2, temozolomide dosing is based on body weight in (kg), at a dose of 3.3 mg/kg/dose.

  • Irinotecan

    Drug

    Irinotecan 50mg/m2/dose IV daily on Days 1-5

  • Dinutuximab

    Drug

    Dinutuximab 17.5mg/m2/dose IV daily on Days 2-5

  • Sargramostim

    Drug

    Sargramostim 250mcg/m2/dose subcutaneous daily on Days 6-12

Treatment groups

31 Participants
are divided into 1 treatment group
Group A: TreatmentOther 5 interventions

Trial outcomes

Primary outcomes

1

NK cells safety and tolerability: Number of participants with treatment-related adverse events and toxicities

Number of participants with treatment-related adverse events and toxicities as assessed by CTCAE v4.0

Time frame
12 months
2

Response to NK Cell treatment as determine by CT/MRI imaging

To estimate the response to treatment, as determined by disease status evaluated using CT/MRI scans through the measuring tool RECIST.

Time frame
24 months
3

Response to NK Cell treatment as determine by MIBG scans imaging

To estimate the response to treatment, as determined by disease status evaluated using MIBG scans through the Curie score system.

Time frame
24 months
4

Response to NK Cell treatment as determine by bone marrow aspiration

To estimate the response to treatment, as determined by disease status evaluated using bone marrow aspiration and biopsy through H\&E stain. RECIST.

Time frame
24 months

Secondary outcomes

1

Toxicity Definition of NK cells

Toxicity will be graded using the CTCAE criteria, version 5.0. All grade 3+ toxicities will be reviewed for attribution.

Time frame
36 months

Other outcomes

1

Assessment of the phenotype of expanded NK cells for neuroblastoma patients

NK cell phenotypes will be measured by mass cytometry (unit of measure= % of nucleated cells)

Time frame
36 months
2

Assessment of function of expanded NK cells for neuroblastoma patients

NK cell functional potency will be measured as cytotoxicity by calcien- AM cytotoxicity assays (unit of measure= % of patietns with complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), or progressive disease (PD) with calculated 95% confidence intervals)

Time frame
36 months
3

In vivo persistence of NK cells after adoptive transfer.

To assess in vivo persistence of expanded NK cells after adoptive transfer by assessing NK cell number and phenotype in peripheral blood using mass cytometry.

Time frame
36 months
4

Correlation of persistence of NK cells after adoptive transfer with clinical outcomes

Clinical outcomes will be assessed by disease response using CT/MRI scans, I-123 metaiodobenzylguanidine (MIBG) scans, and bone marrow aspiration and biopsy

Time frame
36 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Nationwide Children's Hospital

Lead sponsor

Source ClinicalTrials.gov
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