Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)

NCT03224819 | Terminated Early Phase 1 Results FDA Drug

• 2 other identifiers: 201603772017-002980-16
• Study Type: interventional
• Target: 46
• Locations: 3 countries
• Sites: 7

Brief Summary

The primary objectives of this study are to evaluate the safety and tolerability of emerfetamab in adults with relapsed/refractory acute myeloid leukemia (AML) and to estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose \[RP2D\]).

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events

  The severity of each adverse event (AE) was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening and Grade 5 = death due to AE. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal * life threatening * required in patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event.

  From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months.

• Number of Participants With Dose-limiting Toxicities (DLT)

  A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than emerfetamab: * Any treatment-related death; * Grade 4 neutropenia persisting at 42 days after the last infusion in treatment cycle 1; * Grade 3-5 non-hematologic toxicity not clearly resulting from the underlying leukemia with a few protocol-specified exceptions; * Grade 2 or 3 cytokine release syndrome (CRS) meeting any of the criteria listed below: * Grade 2 CRS that does not resolve, with or without intervention to Grade 1 within 7 days; * Grade 3 CRS that does not resolve, with or without intervention to Grade 2 within 5 days, or grade 1 within 7 days; * Grade 3 CRS reported at the initial dose; * Two separate grade 3 CRS events; * Grade 4 CRS occurring during treatment.

  Schedule A: From the start of the first infusion on day 1 until day 14. Schedule B: From the start of the first infusion on day 1 to day 28.

Secondary Outcomes (18)

• Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab

  Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.

• Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab

  Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.

• Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab

  Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion.

• Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab

  Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.

• Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab

  Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.

Study Arms (2)

Dose Escalation

EXPERIMENTAL

The dose-escalation cohorts to estimate the MTD will use 2 schedules of emerfetamab administration: Schedule A (Day 1/Day 5 dosing in 14-day cycles) and Schedule B (once daily dosing for cycle 1 followed by twice weekly dosing in following cycles). For Schedule A the starting dose for the first cohort will be 0.05 μg emerfetamab administered as short term IV infusions on day 1 and day 5. The doses administered for the following cohorts will be recommended by the Dose Level Review Team (DLRT). For Schedule B the starting dose will be 72 μg emerfetamab administered as short-term IV infusions daily (QD) during the 14-day cycle 1 after the 72 μg target dose is found to be relatively safe and tolerable by the DLRT for Schedule A.

Drug: Emerfetamab

Expansion Phase

EXPERIMENTAL

For each schedule, upon completion of the dose escalation cohorts, additional participants may be enrolled to receive emerfetamab at a dose at or below the MTD estimated in the dose escalation cohorts.

Drug: Emerfetamab

Interventions

Emerfetamab DRUG

Administered by intravenous (IV) infusion.

Also known as: AMG 673

Dose Escalation; Expansion Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
• Subjects ≥ 18 years of age at the time of signing consent.
• AML as defined by the World Health Organisation (WHO) Classification persisting or recurring following 1 or more treatment courses except promyelocytic leukemia (APML).
• More than 5% myeloblasts in bone marrow.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

You may not qualify if:

• Known hypersensitivity to immunoglobulins.
• Autologous hematopoietic stem cell transplantation (HSCT) within 6 weeks prior to start of AMG 673 treatment.
• Allogeneic HSCT within 3 months prior to start of AMG 673 treatment.
• Non-manageable graft versus host disease.
• Known positive test for human immunodeficiency virus (HIV).
• Males and females of reproductive potential who are unwilling to practice a highly effective method(s) of birth control while on study through 15 weeks after receiving the last dose of study drug. Acceptable methods of highly effective birth control include sexual abstinence (males, females); vasectomy; bilateral tubal ligation/occlusion; or a condom with spermicide (men) in combination with hormonal birth control or intrauterine device (IUD) (women). Males who are unwilling to abstain from sperm donation while on study through 5 half-lives after receiving the (last \[multiple-dose studies\]) dose of study drug.
• Females who are lactating/breastfeeding or who plan to breastfeed while on study through 15 weeks after receiving the last dose of study drug.
• Females with a positive pregnancy test
• Females planning to become pregnant while on study through 15 weeks after receiving the last dose of study drug.

Sponsors & Collaborators

• Amgen: lead

Study Sites (7)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Klinikum der Ludwig Maximilians Univeritaet

München, 81377, Germany

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Bayesian Model

Study Record Dates

• First Submitted: July 3, 2017
• First Posted: July 21, 2017
• Study Start: September 7, 2017
• Primary Completion: December 28, 2020
• Study Completion: December 28, 2020
• Last Updated: September 1, 2023
• Results First Posted: September 1, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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 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.
• 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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.

Locations

US (4); DE (1); AU (2)