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): 96
• 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
    • Universitätsklinikum 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
• Genders Eligible for Study: All

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	Time Frame
Subject incidence of adverse events (AEs) as a measure of safety	36 months
Subject incidence of dose-limiting toxicities (DLTs) as a measure of safety	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of anti-AMG 330 antibody formation	36 months
Efficacy parameter: Response rate in subjects with relapsed/refractory acute myeloid leukemia	36 months
Efficacy parameter: Response rate in subjects with myelodysplastic syndrome	36 months
Efficacy parameter: Response rate in subjects with minimal residual disease (MRD) positive acute myeloid leukemia	36 months
Efficacy parameter: Duration of response	36 months
Efficacy parameter: Time to progression	36 months
Efficacy parameter: Time to response	36 months
Pharmacokinetic parameter: Half-life of AMG 330	32 months
Pharmacokinetic parameter: Steady state concentration of AMG 330	32 months
Pharmacokinetic parameter: Volume of distribution of AMG 330	32 months
Pharmacokinetic parameter: Clearance of AMG 330	32 months

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 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 (Estimate): August 11, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)