NCT03209869

Brief Summary

Subjects with relapsed or refractory neuroblastoma and osteosarcoma will receive ex-vivo expanded and activated natural killer (NK) cells from a haploidentical donor in conjunction with the immunocytokine, hu14.18-IL2.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Mar 2018

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 13, 2017

Completed
23 days until next milestone

First Posted

Study publicly available on registry

July 6, 2017

Completed
8 months until next milestone

Study Start

First participant enrolled

March 12, 2018

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 7, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 7, 2022

Completed
Last Updated

September 13, 2022

Status Verified

September 1, 2022

Enrollment Period

4.5 years

First QC Date

June 13, 2017

Last Update Submit

September 12, 2022

Conditions

Outcome Measures

Primary Outcomes (2)

  • Safety: Incidence of treatment-emergent adverse events of treatment with AENK cells and hu14.18-IL2

    Safety will be assessed by quantifying adverse events ≥ grade 3, using CTCAE (v.5), with certain pre-defined exceptions based on known, transient, reversible, clinically manageable toxicities of the chemotherapy and hu14.18-IL2.

    up to 28 days after final dose of EA-NK cells or hu14.18-IL2, whichever occurs last

  • Safety: Incidence of any grade acute or chronic GVHD

    Safety will be assessed by monitoring for any grade acute or chronic GVHD.

    up to 21 days after final dose of EA-NK cells or hu14.18-IL2, whichever occurs last

Secondary Outcomes (9)

  • Efficacy: Progression free survival

    up to12 months after final dose of EA-NK cells or hu14.18-IL2, whichever occurs last

  • Efficacy: Overall survival

    up to12 months after final dose of EA-NK cells or hu14.18-IL2, whichever occurs last

  • Efficacy: Objective tumor response (SD + CR + PR)

    up to12 months after final dose of EA-NK cells or hu14.18-IL2, whichever occurs last

  • Longevity of EA-NK cells in vivo

    28 days

  • Immunocytokine (hu14.18-IL2) serum levels given as daily infusions for 7 consecutive days

    up to 28 days after last hu14.18-IL2 infusion

  • +4 more secondary outcomes

Study Arms (1)

Single arm

EXPERIMENTAL

All subjects will receive Ex vivo Expanded and Activated Haploidentical Donor NK Cells + hu14.18-IL2

Biological: Ex vivo Expanded and Activated Haploidentical Donor NK CellsBiological: Hu14.18-IL2

Interventions

Haploidentical donor NK cells that are expanded and activated under current GMP conditions using K562-mbIL15-41BBL.

Also known as: EANK cells
Single arm
Hu14.18-IL2BIOLOGICAL

The immunocytokine, hu14.18-IL2, is a fusion protein comprised of one molecule of the anti-GD2 humanized monoclonal antibody, hu14.18, fused to two molecules of the cytokine, interleukin-2.

Also known as: Immunocytokine
Single arm

Eligibility Criteria

Age7 Months - 25 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Relapsed or refractory neuroblastoma
  • Relapsed or refractory Osteosarcoma
  • Karnofsky/Lansky performance score \> 50
  • Life expectancy ≥ 4 months
  • Creatinine clearance or radioisotope GFR ≥ 60 ml/min/1.73m2 OR serum creatinine within normal limits based on age and gender
  • ANC ≥ 750/µL
  • Platelet count ≥ 50,000/µL
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal for age
  • ALT (SCPT) ≤ 5 x upper limit of normal for age
  • Shortening fraction of ≥ 27% by echocardiogram OR Ejection fraction of ≥55% by MUGA
  • No evidence of dyspnea at rest
  • Pulse oximetry \> 94% on room air
  • If PFTs performed, FEV1/FVC must be \> 60%
  • All Osteosarcoma patients must have PFTs performed
  • +13 more criteria

You may not qualify if:

  • Prior history of ventilator support related to lung injury, except for immediately following thoracotomy
  • Symptomatic pleural effusions or ascites
  • \<6 weeks from thoracotomy and \<2 weeks from other major surgery
  • History of anaphylaxis while receiving prior anti-GD2 therapy
  • Pregnant
  • HIV infection
  • Heart failure or uncontrolled cardiac rhythm disturbance
  • Active infection
  • Prior organ allograft
  • Prior allogeneic bone marrow or peripheral blood stem cell transplant
  • Significant serious intercurrent illnesses expected to interfere with the antitumor effect of treatment or to significantly increase the severity of toxicities experienced from treatment
  • Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study.
  • Enrollment in any other treatment study from screening up to 28 days after the last treatment on this study (unless PI judges such enrollment would not interfere with endpoints of this study)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Wisconsin Carbone Cancer Center; UW Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Links

MeSH Terms

Conditions

NeuroblastomaOsteosarcoma

Interventions

lorukafusp alfa

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueNeoplasms, Bone TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueSarcoma

Study Officials

  • Ken DeSantes, MD

    University of Wisconsin, Madison

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 13, 2017

First Posted

July 6, 2017

Study Start

March 12, 2018

Primary Completion

September 7, 2022

Study Completion

September 7, 2022

Last Updated

September 13, 2022

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will not share

Locations