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

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

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 Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndrome; Relapsed/Refractory AML; Minimal Residual Disease Positive AML
• Intervention / Treatment: Drug: AMG 330

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• Germany
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein
  • München, Germany, 81377
    • Klinikum der Universität München Campus Grosshadern
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
• Netherlands
  • Amsterdam, Netherlands, 1007 MB
    • Research Site
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • Research Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)	Drug: AMG 330; 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.
Experimental: Group 2: Minimal Residual Disease Positive (MRD+) AML	Drug: AMG 330; 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.
Experimental: Group 3: Myelodysplastic syndrome (MDS)	Drug: AMG 330; 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.
Experimental: Group 4: R/R AML with alternative pretreatment	Drug: AMG 330; 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.
Experimental: Group 5: R/R AML with alternative dose schedule	Drug: AMG 330; 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	From first dose of IP (Day 1) until the end of study, up to approximately 6 months
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-.	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.	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.	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.	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.	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.	Baseline until the end of study, up to approximately 6 months
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2015
• Primary Completion (Actual): January 9, 2022
• Study Completion (Actual): January 9, 2022

Study Registration Dates

• First Submitted: June 17, 2015
• First Submitted That Met QC Criteria: August 7, 2015
• First Posted (Estimated): August 11, 2015

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Phase 1; Clinical Trial; Amgen; Relapsed/Refractory AML; Oncology/Hematology
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Neoplastic Processes; Myelodysplastic Syndromes; Neoplasm, Residual
• Other Study ID Numbers: 20120252; 2014-004462-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR