The purpose of this dose finding study is to evaluate the safety and efficacy of 2 different dose levels of CLR 131 in children, adolescents and young adults with relapsed or refractory high-grade glioma (HGG).
This study is designed to further evaluate the safety and tolerability of CLR 131 at the selected doses in children, adolescents and young adults with relapsed or refractory malignant high-grade glioma. It will also determine the therapeutic activity defined as progression free survival and overall survival, antitumor activity (treatment response) defined as the reduction in tumor volume and identify the recommended Phase 2/3 dose of CLR 131 in children, adolescents and young adults with relapsed or refractory HGG.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
CLR 131 will be administered IV (intravenously) at a dose based on patients' BSA
Stanford University
Palo Alto, California, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Safety Evaluation of CLR 131
Will be assessed by physical examination, performance status, vital signs, laboratory changes over time, and adverse events. Evaluations will use a nonparametric Wilcoxon Signed Rank test and a linear mixed effects modeling will be conducted to evaluate longitudinal changes.
Time frame: Assessed throughout the study to 1-year post-infusion follow-up period
Efficacy Evaluation for Progression Free Survival
To determine the therapeutic activity defined as Progression Free Survival (PFS) using Kaplan Meier estimator. PFS is defined as the time from arm assignment until disease progression or death.
Time frame: Day 84 post-infusion follow-up period through 3 years following completion of treatment.
Treatment Response of CLR 131
Determine antitumor activity (treatment response) defined as the reduction in tumor volume, measured by MRI scans acquired as FLAIR images and based on the RAPNO criteria for responses.
Time frame: From date of arm assignment until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 48 months.
Dose Determination for CLR 131
Identify the recommended Phase 2/3 dose of CLR 131 in relapsed pHGG patients based on both safety and efficacy assessments as defined by the primary endpoints concluded from this study.
Time frame: From date of arm assignment until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 48 months.
Dosimetry Evaluation for Total Body and Organ
To determine total body and organ dosimetry, together, of CLR 131 in relapsed pHGG patients, measured by conjugate planar whole-body imaging and/or blood collection drawn for radiologic dosimetry analysis for a subset of patients. Organ time/activity integrals will be entered into OLINDA/EXM software to produce total body and organ dosimetry values for CLR 131.
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Philadelphia, Pennsylvania, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Texas Children's Cancer Center, Baylor College of Medicine
Houston, Texas, United States
University of Wisconsin, Carbone Cancer Center
Madison, Wisconsin, United States
Hospital for Sick Children
Toronto, Ontario, Canada
Time frame: 4 hours post-infusion and concluding 4 weeks post-initial imaging
Tumor Response to CLR 131
Determine the tumor uptake of CLR 131 and utility of SPECT/CT as a potential diagnostic for response. Images will be reconstructed using quantitative SPECT reconstruction methods with compensation for attenuation, scatter and the full collimator-detector response including septal penetration and scatter. A registered CT image will be used as the attenuation map for the SPECT images. Image data will be converted to activity per cubic centimeters using a sensitivity measurement made using a point source in air.
Time frame: 4 hours post-infusion and concluding 4 weeks post-initial imaging