The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma.
This is a two-part, multi-center first in human study of ION251 in up to 80 participants. Part 1 will use a 3+3 dose-escalation scheme in sequential cohorts to determine the MTD and RP2D during repeated 28-day treatment cycles. MTD will be determined by the number of participants with AEs meeting the dose-limiting toxicity (DLT) criteria during Cycle 1. The MTD determined in Part 1 will be used with other variables to inform a RP2D for participants proceeding to Part 2 for further assessments in the safety, tolerability and anti-myeloma activity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
ION251 administered by IV infusion
University of California San Diego Moores Cancer Center
La Jolla, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
UCLA Rrmc
Los Angeles, California, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Maximum-Tolerated Dose (MTD)
MTD is defined as the maximum dose at which ≤ 1 of 3 evaluable participants experiences a dose-limiting toxicity (DLT) within Cycle 1 and there are 2 of 3 or 2 of 6 evaluable participants in the next higher-dose level experiencing a DLT within Cycle 1. If no dose in the dose-escalation has 2 of 3 or 2 of 6 evaluable participants experiencing a DLT, the highest dose level is considered the MTD
Time frame: Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)
Recommended Phase 2 Dose (PR2D)
RP2D is chosen based on the dose response and exposure-response analyses of the pooled clinical PK, PD, safety results, and anti-myeloma activity from both Part 1 and Part 2
Time frame: Up to 28 days from the last dose of study drug
Safety and Tolerability as Measured by the Incidence of TEAEs
Time frame: Up to 28 days from the last dose of study drug
Incidence of Abnormal Laboratory Values and Vital Signs
Time frame: Up to 28 days from the last dose of study drug
Cmax: Maximum Observed Concentration ION251
Time frame: From Baseline up to 28 days from the last dose of study drug
AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251
Time frame: From Baseline up to 28 days from the last dose of study drug
t1/2: Distribution Half-life of ION251
Time frame: From Baseline up to 28 days from the last dose of study drug
Trough Concentration of ION251
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Washington University School of Medicine in Saint Louis
St Louis, Missouri, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Time frame: From Baseline up to 28 days from the last dose of study drug
Urine 0-24 Hour (hr) Excretion of ION251
Time frame: Up to 12 months from the last dose of study drug