A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies

Phase 1

Terminated

Conditions: Myelodysplastic Syndrome
Minimal Residual Disease Positive AML
Relapsed/Refractory AML

Interventions: Drug: AMG 330

Registration Number: NCT02520427

Lead Sponsor: Amgen

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 95

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group 3: Myelodysplastic syndrome (MDS)	AMG 330	-
Group 5: R/R AML with alternative dose schedule	AMG 330	-
Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)	AMG 330	-
Group 4: R/R AML with alternative pretreatment	AMG 330	-
Group 2: Minimal Residual Disease Positive (MRD+) AML	AMG 330	-

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	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	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.
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)	Day 1 to Day 14	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.

Secondary Outcome Measures

Name	Time	Method
Response Rate in Participants With R/R AML	From first dose of IP (Day 1) until the end of study, up to approximately 6 months	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).
Event-free Survival	From first dose of IP (Day 1) until the end of study, up to approximately 6 months	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.
28 Day Infusion Duration: CL of AMG 330	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)
Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation	Baseline until the end of study, up to approximately 6 months	Number of participants with a binding anti-body positive result at any timepoint post-baseline who had a negative or no result at baseline.
Response Rate in Participants With MRD-positive AML	From first dose of IP (Day 1) until the end of study, up to approximately 6 months	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-.
Response Rate in Participants With MDS	From first dose of IP (Day 1) until the end of study, up to approximately 6 months	Response for participants with MDS was defined as the percentage of participants with CR or marrow complete remission per IWG.
Duration of Response	From first dose of IP (Day 1) until the end of study, up to approximately 6 months	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.
14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330	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)
14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330	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	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	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	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)
Time to Response	From first dose of IP (Day 1) until the end of study, up to approximately 6 months	Time to response was defined as the interval from the first administration of AMG 330 to the first documentation of response.
14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330	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)
Overall Survival	Baseline until the end of study, up to approximately 6 months	Overall survival was defined as the time from enrollment until death due to any cause.
28 Day Infusion Duration: t1/2 z of AMG 330	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)

Trial Locations

Locations (10): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Research Site
🇳🇱
Amsterdam, Netherlands
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
Princess Margaret Cancer Centre
🇨🇦
Toronto, Ontario, Canada
Klinikum der Universität München Campus Grosshadern
🇩🇪
München, Germany
Universitatsklinikum Ulm
🇩🇪
Ulm, Germany
Erasmus Medisch Centrum
🇳🇱
Rotterdam, Netherlands
Universitätsklinikum Schleswig-Holstein
🇩🇪
Kiel, Germany
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States