Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Treatment of Relapsed or Refractory Neuroblastoma With Expanded Haploidentical NK Cells and Hu14.18-IL2

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03209869
Recruitment Status : Recruiting
First Posted : July 6, 2017
Last Update Posted : November 19, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Solving Kids’ Cancer
Midwest Athletes Against Childhood Cancer, Inc. (MACC Fund)
Wade's Army
The Catherine Elizabeth Blair Memorial Foundation / GWCF
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE June 13, 2017
First Posted Date  ICMJE July 6, 2017
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE March 12, 2018
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2017)
Assess safety of EA-NK cells administered to lymphodepleted patients with relapsed or refractory neuroblastoma followed by daily infusions of hu14.18-IL2 for 7 days, defined as any CTCAE (v. 4.03) grade 3 or 4 toxicity with certain pre-defined exceptions [ Time Frame: 28 days after EA-NK infusion ]
Evaluation of toxicities defined as any CTCAE (v. 4.03) grade 3 or 4 toxicity with certain pre-defined exceptions based on known, transient, reversible, clinically manageable toxicities of the chemotherapy and hu14.18-IL2
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
  • Anti-tumor effect of treatment; progression free survival [ Time Frame: 12 months from final EA-NK cell infusion ]
    Progression free survival. Time from randomization until disease progression or death, up to 12 months from final EA-NK cell infusion.
  • Anti-tumor effect of treatment; objective response [ Time Frame: 12 months from final EA-NK cell infusion ]
    Objective response (SD + CR + PR)
  • Anti-tumor effect of treatment; overall survival [ Time Frame: 12 months from final EA-NK cell infusion ]
    Overall survival. Time from randomization until death from any cause, up to 12 months from final EA-NK cell infusion.
  • Longevity of EA-NK cells in vivo [ Time Frame: 28 days ]
    Evaluating the survival of EA-NK cells in the subject using flow cytometric analysis of donor-only antigens
  • Immunocytokine (hu14.18-IL2) serum levels given as daily infusions for 7 consecutive days [ Time Frame: 28 days after last hu14.18-IL2 infusion ]
    ELISA
  • Immunogenicity of hu14.18-IL2 given as daily infusions for 7 consecutive days [ Time Frame: 28 days after last hu14.18-IL2 infusion ]
    ELISA
  • Immune Reconstitution - Frequency of cell subset [ Time Frame: 28 days after hu14.18-IL2 infusion ]
    Analysis of NK cell and T cell subsets using flow cytometry. The frequencies of each cell subset, as determined by immune cell phenotyping will be summarized in tabular format. Ninety five percent confidence intervals will be constructed using the Wilson score method.
  • Immune Reconstitution - Percentage of cell subset [ Time Frame: 28 days after hu14.18-IL2 infusion ]
    Analysis of NK cell and T cell subsets using flow cytometry. The percentages of each cell subset, as determined by immune cell phenotyping will be summarized in tabular format. Ninety five percent confidence intervals will be constructed using the Wilson score method.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2017)
  • Anti-tumor effect of treatment; progression free survival [ Time Frame: 12 months from final EA-NK cell infusion ]
    Progression free survival. Time from randomization until disease progression or death, up to 12 months from final EA-NK cell infusion.
  • Anti-tumor effect of treatment; objective response [ Time Frame: 12 months from final EA-NK cell infusion ]
    Objective response (SD + CR + PR)
  • Anti-tumor effect of treatment; overall survival [ Time Frame: 12 months from final EA-NK cell infusion ]
    Overall survival. Time from randomization until death from any cause, up to 12 months from final EA-NK cell infusion.
  • Longevity of EA-NK cells in vivo [ Time Frame: 12 months ]
    Evaluating the survival of EA-NK cells in the subject using flow cytometric analysis of donor-only antigens
  • Immunocytokine (hu14.18-IL2) serum levels given as daily infusions for 7 consecutive days [ Time Frame: 28 days after last hu14.18-IL2 infusion ]
    ELISA
  • Immunogenicity of hu14.18-IL2 given as daily infusions for 7 consecutive days [ Time Frame: 28 days after last hu14.18-IL2 infusion ]
    ELISA
  • Immune Reconstitution - Frequency of cell subset [ Time Frame: 28 days after hu14.18-IL2 infusion ]
    Analysis of NK cell and T cell subsets using flow cytometry. The frequencies of each cell subset, as determined by immune cell phenotyping will be summarized in tabular format. Ninety five percent confidence intervals will be constructed using the Wilson score method.
  • Immune Reconstitution - Percentage of cell subset [ Time Frame: 28 days after hu14.18-IL2 infusion ]
    Analysis of NK cell and T cell subsets using flow cytometry. The percentages of each cell subset, as determined by immune cell phenotyping will be summarized in tabular format. Ninety five percent confidence intervals will be constructed using the Wilson score method.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Relapsed or Refractory Neuroblastoma With Expanded Haploidentical NK Cells and Hu14.18-IL2
Official Title  ICMJE Treatment of Relapsed or Refractory Neuroblastoma With Ex-Vivo Expanded and Activated Haploidentical NK Cells and Hu14.18-IL2
Brief Summary Subjects with relapsed or refractory neuroblastoma will receive ex-vivo expanded and activated natural killer (NK) cells from a haploidentical donor in conjunction with the immunocytokine, hu14.18-IL2.
Detailed Description

Natural Killer cells, a type of white blood cell, circulate around the body and kill abnormal cells (cells that are malignant, damaged or infected with virus). Sometimes cancer cells adapt to the body's own NK cells and are able to avoid being killed by them. This clinical trial uses two strategies to overcome the cancer cells' ability to avoid NK cell-mediated death.

The first strategy involves giving NK cells from another individual to the patient (in other words, donor- or haploidentical-NK cells). This is done because NK cells from an individual who is haploidentical (half-matched genetic make-up) are still able to effectively kill the cancer cells. Unfortunately, only a limited number of NK cells can be obtained from a donor. So, to increase the number of cancer-killing NK cells that will be given to the patient, the donor NK cells will first be grown in a sterile laboratory environment and allowed to multiply many-fold before they are infused into the patient. This growing process also activates the donor NK cells, which increases their ability to kill cancer cells.

The second strategy to overcome the cancer cells' ability to avoid NK cell-mediated death is to administer the immunocytokine, hu14.18-IL2, every day for seven days after infusion of the donor NK cells. The antibody portion (hu14.18) of the immunocytokine molecule "flags" the neuroblastoma cells for destruction by NK cells and the cytokine portion (IL2) further activates the NK cells (as well as other anti-tumor immune effector cells).

Since the donor NK cells are from a haploidentical individual, they are different enough to be recognized as foreign cells and will be killed immediately ("rejected") by the patients own immune system unless the immune system is restrained. So, to allow the donor NK cells time to kill neuroblastoma cells before they are "rejected", a chemotherapy regimen is first given to the patient to temporarily restrain the patient's own immune system. This also allows "room" for the donor NK cells to live, multiply and function.

Four courses of treatment are planned for each subject. Each course of treatment will be approximately one month long and involves a week of chemotherapy followed by infusion of donor NK cells. Beginning the day after the donor NK cell infusion, hu14.18-IL2 is infused over four hours for seven consecutive days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroblastoma
  • Relapsed Neuroblastoma
  • Recurrent Neuroblastoma
Intervention  ICMJE
  • Biological: Ex vivo Expanded and Activated Haploidentical Donor NK Cells
    Haploidentical donor NK cells that are expanded and activated under current GMP conditions using K562-mbIL15-41BBL.
    Other Name: EANK cells
  • Biological: Hu14.18-IL2
    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.
    Other Name: Immunocytokine
Study Arms  ICMJE Experimental: Single arm
All subjects will receive Ex vivo Expanded and Activated Haploidentical Donor NK Cells + hu14.18-IL2
Interventions:
  • Biological: Ex vivo Expanded and Activated Haploidentical Donor NK Cells
  • Biological: Hu14.18-IL2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2017)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2021
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Relapsed or refractory neuroblastoma
  • 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
  • CNS toxicity ≤ Grade 2
  • Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsant therapy
  • >100 days after autologous stem cell infusion following myeloablative therapy
  • > 2 weeks since chemotherapy
  • ≥ 6 months if prior craniospinal axis XRT (> 50%)
  • ≥ 6 months if > 50% radiation of pelvis
  • ≥ 6 weeks after therapeutic 131-I-MIBG
  • Informed consent obtained (patient or legal representative)
  • Women of reproductive potential must have negative pregnancy test and be willing to use effective birth control method
  • Suitable haploidentical donor must be available
  • No evidence of CNS (central nervous system) disease in patients with a history of CNS disease
  • > 1 week since growth factor(s)

Exclusion Criteria:

  • Prior history of ventilator support related to lung injury
  • Symptomatic pleural effusions or ascites
  • < 2 weeks after 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 anti-tumor effect of treatment or to significantly increase the severity of toxicities experienced for 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 clinical study from screening up to Day 28 after the last treatment on this study (unless PI judges such enrollment would not interfere with endpoints of this study)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Months to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jenny Weiland, CCRP 608-890-8070 PedsHemOncResearch@lists.wisc.edu
Contact: Celeste Matsushima 608-890-8069
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03209869
Other Study ID Numbers  ICMJE UW16009
P30CA014520 ( U.S. NIH Grant/Contract )
2016-1195 ( Other Identifier: Institutional Review Board )
A536755 ( Other Identifier: UW Madison )
SMPH/PEDIATRICS/PEDIATRICS ( Other Identifier: UW Madison )
NCI-2017-01267 ( Registry Identifier: NCI Trial ID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Solving Kids’ Cancer
  • Midwest Athletes Against Childhood Cancer, Inc. (MACC Fund)
  • Wade's Army
  • The Catherine Elizabeth Blair Memorial Foundation / GWCF
Investigators  ICMJE
Principal Investigator: Ken DeSantes, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP