Clinical trial NCT02520427: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies
Official title: A Phase 1 First-in-human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 330 Administered as Continuous Intravenous Infusion in Subjects With Myeloid Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Relapsed/Refractory AML
Minimal Residual Disease Positive AML
Myelodysplastic Syndrome
Keywords: Amgen
Phase 1
Clinical Trial
Oncology/Hematology
Relapsed/Refractory AML
Immunotherapy
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-08-11
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

* Informed consent provided
* 18 years or older
* Relapsed/refractory AML: AML as defined by the WHO Classification persisting or recurring following one or more treatment courses except promyelocytic leukemia (APML)

Exclusion criteria:

* Active extramedullary AML in testes or central nervous system (CNS)
* Known hypersensitivity to immunoglobulins or to any other component of the IP formulation (eg, sucrose, captisol, potassium, polysorbate 80, citrate, lysine)
* Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for \> 1 years before screening

Primary outcomes:
measure: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
timeFrame: Day 1 to Day 14
measure: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
timeFrame: 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
Secondary outcomes:
measure: Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation
timeFrame: Baseline until the end of study, up to approximately 6 months
measure: Response Rate in Participants With R/R AML
timeFrame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
measure: Response Rate in Participants With MRD-positive AML
timeFrame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
measure: Response Rate in Participants With MDS
timeFrame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
measure: Duration of Response
timeFrame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
measure: Time to Response
timeFrame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
measure: Event-free Survival
timeFrame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
measure: Overall Survival
timeFrame: Baseline until the end of study, up to approximately 6 months
measure: 14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330
timeFrame: 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)
measure: 28 Day Infusion Duration: t1/2 z of AMG 330
timeFrame: 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)
measure: 14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330
timeFrame: 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)
measure: 28 Day Infusion Duration: Css After End of Infusion of AMG 330
timeFrame: 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)
measure: 14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330
timeFrame: 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)
measure: 28 Day Infusion Duration: Vz of AMG 330
timeFrame: 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)
measure: 14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330
timeFrame: 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)
measure: 28 Day Infusion Duration: CL of AMG 330
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: Research Site
state: California
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Klinikum der Universität München Campus Grosshadern
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Amsterdam
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: