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Trial record 1 of 1 for:    NCT02271711
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Expanded Natural Killer Cell Infusion in Treating Younger Patients With Recurrent/Refractory Brain Tumors

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ClinicalTrials.gov Identifier: NCT02271711
Recruitment Status : Recruiting
First Posted : October 22, 2014
Last Update Posted : May 23, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE October 17, 2014
First Posted Date  ICMJE October 22, 2014
Last Update Posted Date May 23, 2019
Actual Study Start Date  ICMJE March 17, 2015
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
Maximum tolerated dose (MTD) of natural killer (NK) cells [ Time Frame: 4 weeks ]
Defined as the highest dose studied in which 6 patients have been treated at most 1 patient with dose limiting toxicities are observed. Toxicities will be summarized by tabulation in terms of type, grade and attribution for each dose level of each group of patients studied at the end of the trial.
Original Primary Outcome Measures  ICMJE
 (submitted: October 20, 2014)
Maximum Tolerated Dose (MTD) of Autologous Natural Killer (NK) Cells [ Time Frame: 4 weeks ]
Maximum Tolerated Dose (MTD) is maximum dose at which fewer than one-third of patients experience a Dose Limiting Toxicity (DLT) during cycle 1 of therapy. MTD defined as highest dose studied in which six patients have been treated and at most one patient with DLTs are observed.
Change History Complete list of historical versions of study NCT02271711 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Activation status of NK cells [ Time Frame: Up to 30 days after the last infusion in course 3 ]
    Determined by flow-based activation assay determining cluster of differentiation (CD)107a expression of NK cells in response to standardized targets.
  • Persistence of NK cells [ Time Frame: Up to 30 days after the last infusion in course 3 ]
    Peripheral blood and cerebrospinal fluid (CSF) will be obtained before therapy, during the NK cell treatment period, and after NK cell treatment.
  • Function of NK cells [ Time Frame: Up to 30 days after the last infusion in course 3 ]
    Assessed by cell lysis of standardized targets.
  • Response of medulloblastoma to NK cells [ Time Frame: Up to 30 days after the last infusion in course 3 ]
    Antitumor activity will be described for each group of patients based on imaging and cytology. Clinical response will be correlated with NK cell persistence in vivo, cytokine levels, and expression of activation markers.
  • Feasibility of NK cell manufacturing [ Time Frame: Up to 12 weeks ]
    If analysis shows < 50% successful product generation after at least six patients have been enrolled, the study will be temporarily stopped to address possible changes in the manufacturing process.
  • Feasibility of delivering NK cells [ Time Frame: Up to 12 weeks ]
    Therapy will be considered feasible if at least 2/3 of subjects treated receive at least 21 of the planned 27 NK cell infusions.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2014)
Antitumor Activity of Autologous NK Cell Administration [ Time Frame: 7 days after 3, 4 week cycles ]
Antitumor activity based on imaging and cytology. Measurable disease defined as presence of at least one lesion that can be accurately measured in two dimensions, each of which measure at least 10 mm: product of longest diameter and longest perpendicular diameter. Evaluable disease defined as at least one lesion that cannot be accurately measured in at least one dimension, or positive CSF cytology.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Expanded Natural Killer Cell Infusion in Treating Younger Patients With Recurrent/Refractory Brain Tumors
Official Title  ICMJE Phase I Study of Intraventricular Infusions of Autologous Ex Vivo-Expanded NK Cells in Children With Recurrent/Refractory Malignant Posterior Fossa Tumors of the Central Nervous System. NOAH's (New Opportunity, Advancing Hope) Protocol
Brief Summary This phase I trial studies the side effects and best dose of expanded natural killer cells in treating younger patients with brain tumors that have come back or do not respond to treatment. Infusing a particular type of a patient's own white blood cells called natural killer cells that have been through a procedure to expand (increase) their numbers may work in treating patients with recurrent/refractory brain tumors.
Detailed Description

PRIMARY OBJECTIVES:

I. To establish the safety, feasibility, efficacy, and maximum tolerated dose (MTD) of administering autologous natural killer (NK) cells that have been propagated ex vivo with artificial antigen-presenting cells (aAPC) and administered directly into the ventricle in recurrent /refractory malignant posterior fossa tumors.

SECONDARY OBJECTIVES:

I. To assess the antitumor activity based on imaging and cytology of autologous NK cell locoregional administration directly into the lateral or fourth ventricle.

II. To determine the persistence of adoptively-transferred expanded NK cells (as performed with excess NK cells, via optional correlative studies).

III. Determine the immunophenotype and function of expanded NK cells. IV. Determine the overall response of medulloblastoma to NK-cell therapy. V. Correlate NK cell persistence, phenotype, and function with overall response.

OUTLINE: This is a dose-escalation study.

Patients receive autologous expanded NK cells intravenously (IV) into the ventricle over 3 minutes once weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may continue treatment at the discretion of the treating physician if pseudo-progression or benefit of slowed progression is suspected.

After completion of study treatment, patients are followed up within 30 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Childhood Medulloblastoma
  • Recurrent Ependymoma
  • Recurrent Medulloblastoma
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Natural Killer Cell Therapy
    Given autologous ex-vivo expanded NK cells IV
Study Arms  ICMJE Experimental: Treatment (autologous ex vivo-expanded NK cells)
Patients receive autologous expanded NK cells IV into the ventricle over 3 minutes once weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may continue treatment at the discretion of the treating physician if pseudo-progression or benefit of slowed progression is suspected.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Biological: Natural Killer Cell Therapy
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: October 20, 2014)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2020
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis: patients with recurrent/refractory medulloblastoma (MB), atypical teratoid (AT)/rhabdoid tumors (RT) or ependymoma involving the brain and/or spine at original diagnosis or relapse; they must have histological verification at diagnosis and/or relapse; patient must have presented with these tumors in the posterior fossa (PF) or relapsed in the PF
  • Patient must have either measurable or evaluable tumor
  • Presence of or determined by neurosurgery to be a candidate for an implanted catheter in the ventricles to receive NK cell infusion
  • Life expectancy of at least 12 weeks in opinion of principal investigator (PI) and/or designee
  • Lansky score of 50 or greater if =<16 years of age or a Karnofsky score of 50 or greater if > 16 years of age (NOTE: patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score)
  • Neurologic deficits must have been relatively stable for a minimum of 1 week prior to study enrollment
  • Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
  • Patient must be 4 weeks off any palliative radiation or craniospinal radiation
  • Absolute neutrophil count (ANC) of >= 1000/uL
  • Platelet count of >= 30,000
  • Hemoglobin of >= 9.0 g/dl
  • Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants
  • Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent

Exclusion Criteria:

  • Enrolled in another treatment protocol
  • Evidence of untreated infection
  • Extra-cranial metastasis
  • Chronic corticosteroid dependence (except replacement therapy)
  • Extensive disease, disease location, and/or co-morbid condition that the PI or designee considers unsafe for surgical intervention of NK cell infusion
  • Pregnant or lactating women
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Soumen Khatua 713-792-3280 skhatua@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02271711
Other Study ID Numbers  ICMJE 2013-0765
NCI-2014-02677 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2013-0765 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
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 Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Soumen Khatua M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date May 2019

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