This phase I trial studies the side effects and best dose of pomalidomide in treating younger patients with tumors of the brain or spine (central nervous system) that have come back or are continuing to grow. Pomalidomide may interfere with the ability of tumor cells to grow and spread and may also stimulate the immune system to kill tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of pomalidomide, in children from \>= 3 years to \< 21 years of age with recurrent, progressive or refractory central nervous system (CNS) tumors when given once daily for 21 consecutive days of a 28-day course. II. To describe the toxicity profile and dose-limiting toxicities of pomalidomide in children from \>= 3 years to \< 21 years of age with recurrent, progressive or refractory CNS tumors. III. To characterize the pharmacokinetics of pomalidomide when administered orally in children from \>= 3 years old to \< 21 years of age with recurrent, progressive or refractory CNS tumors and study the association of pharmacokinetic (PK) parameters with age and steroid use. SECONDARY OBJECTIVES: I. To explore the preliminary efficacy of pomalidomide in this patient population as defined by radiographic response rate, duration of response, and event-free survival (EFS) within the confines of a Phase 1 study. \*For the purposes of this study, long-term stable disease will be considered a response (defined as stable disease for \>= 6 courses). II. To investigate a relationship between pomalidomide dose and exposure with radiographic response and changes in immune function (for example, T-cell subsets, natural killer \[NK\] cell activity, granzyme B and circulating levels of IL-12, IL-2, IL-15, GM-CSF). OUTLINE: This is a dose-escalation study. Patients receive pomalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Children's Hospital Los Angeles
Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
National Cancer Institute
Rockville, Maryland, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
...and 2 more locations
Maximum tolerated dose/recommended phase II dose of pomalidomide
Will be defined as the highest dose level at which 6 patients have been treated with at most 1 experiencing dose-limiting toxicity and the next higher dose level has been determined to be too toxic (\>= 2 dose-limiting toxicity). All safety data will be presented by dose cohort (intended dose) within each stratum separately. Adverse events will be tabulated by grade and attribution to the study agent.
Time frame: Up to 28 days
Pharmacokinetics parameters of pomalidomide
Population estimates of pharmacokinetics parameters for pomalidomide will be estimated, and intra- and inter-subject variability of these parameters will be characterized. The effect of demographics/covariates (e.g., age, body weight, gender, prior treatment and use of concomitant medications, etc.) on the pharmacokinetics of pomalidomide will be evaluated. Descriptive statistics provided as appropriate. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose day 1 of course 1; 1 sample pre-dose any day between days 3-21 of course 1
Response rate (complete response, partial response, and stable disease)
The response rate will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided for the entire trial cohort as well as for each stratum separately and will be summarized by each response category (i.e., complete response, partial response, stable disease and progressive disease). Descriptive summaries of response per dose level within each stratum may also be provided.
Time frame: Up to 2 years
Duration of response
Assessed using the Kaplan-Meier method to calculate the median time as well as the proportion remaining event free at given time points. The corresponding 95% confidence intervals will be presented. All results will be presented by stratum as well as combined.
Time frame: The time from the initial documented response (complete response, partial response or long-term stable disease) to the first confirmed progressed disease, assessed up to 2 years
Event-free survival
Assessed using the Kaplan-Meier method to calculate the median event-free survival as well as the proportion remaining event free at given time points. The corresponding 95% confidence intervals will be presented. All results will be presented by stratum as well as for the entire cohort.
Time frame: The time from study enrollment until the time of progressive disease, second-(ary) malignancy or death from any cause on study treatment, assessed up to 2 years
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