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.
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
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Correlative studies
Given autologous ex-vivo expanded NK cells IV
M D Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose (MTD) of natural killer (NK) cells
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.
Time frame: 4 weeks
Activation status of NK cells
Determined by flow-based activation assay determining cluster of differentiation (CD)107a expression of NK cells in response to standardized targets.
Time frame: Up to 30 days after the last infusion in course 3
Persistence of NK cells
Peripheral blood and cerebrospinal fluid (CSF) will be obtained before therapy, during the NK cell treatment period, and after NK cell treatment.
Time frame: Up to 30 days after the last infusion in course 3
Function of NK cells
Assessed by cell lysis of standardized targets.
Time frame: Up to 30 days after the last infusion in course 3
Response of medulloblastoma to NK cells
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.
Time frame: Up to 30 days after the last infusion in course 3
Feasibility of NK cell manufacturing
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.
Time frame: Up to 12 weeks
Feasibility of delivering NK cells
Therapy will be considered feasible if at least 2/3 of subjects treated receive at least 21 of the planned 27 NK cell infusions.
Time frame: Up to 12 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.