The purpose of this First-in-Human Phase 1 study is to determine if AMG 330 given as a continuous IV infusion is safe and tolerable in adult subjects that have myeloid malignancies, and to determine the maximum tolerated dose and/or a biologically active dose. The study will be conducted in multiple sites and test increasing doses of AMG 330. The safety of subjects will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
95
0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Research Site
Duarte, California, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
A participant was not DLT-evaluable if they dropped out before completion of the DLT window (14 days) for reasons other than an adverse event related to study drug or the participant had not received investigational product (IP) treatment for at least 14 days at the target dose for a 3- or 4-week cycle or at least 7 days at a target dose for a 2- week cycle. Furthermore, following drug interruptions, if a participant was unable to complete 2 repeat cycles for reasons other than DLT, the participant was not DLT evaluable.
Time frame: Day 1 to Day 14
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
The severity of TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. The general guideline for assessment ranged from Grade 1 to 5, with higher grades indicating a worse outcome, and included: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death.
Time frame: Day 1 until 30 days after last dose. Median duration of treatment was: Group 1 - 29.0 days; Group 2 - 29.0 days; Group 3 - 49.50 days; Group 4 - 23.50 days
Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation
Number of participants with a binding anti-body positive result at any timepoint post-baseline who had a negative or no result at baseline.
Time frame: Baseline until the end of study, up to approximately 6 months
Response Rate in Participants With R/R AML
Response for participants with R/R AML was defined as the percentage of participants with complete response (CR)/complete remission with incomplete count recovery (CRi)/morphologic leukemia-free state (MLFS) \[per modified international working group (IWG) criteria\] or complete remission with partial hematologic recovery (CRh).
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
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University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Universitätsklinikum Schleswig-Holstein
Kiel, Germany
Klinikum der Universität München Campus Grosshadern
München, Germany
Universitatsklinikum Ulm
Ulm, Germany
Research Site
Amsterdam, Netherlands
...and 1 more locations
Response Rate in Participants With MRD-positive AML
Response for participants with MRD-positive AML was defined as the percentage of participants with a conversion from MRD+ status with 0.1% threshold to CRMDR- or CRiMD-.
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Response Rate in Participants With MDS
Response for participants with MDS was defined as the percentage of participants with CR or marrow complete remission per IWG.
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Duration of Response
Duration of response was defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse, disease progression, or death due to any cause, whichever occurs first.
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Time to Response
Time to response was defined as the interval from the first administration of AMG 330 to the first documentation of response.
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Event-free Survival
Event-free survival was defined as the interval from first administration of AMG 330 to the earliest of date of treatment failure, relapse for responders, or death due to any cause.
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Overall Survival
Overall survival was defined as the time from enrollment until death due to any cause.
Time frame: Baseline until the end of study, up to approximately 6 months
14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330
Time frame: 14 day infusion duration: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: t1/2 z of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: Css After End of Infusion of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: Vz of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 day)
14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: CL of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)