Safety, Tolerability, PK, PD, and Efficacy of AMG 427 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

NCT03541369 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 20170528BB-IND 1384402018-001389-40
• Study Type: interventional
• Target: 64
• Locations: 6 countries
• Sites: 16

Brief Summary

Evaluate the safety and tolerability of AMG 427 in adult subjects with relapsed/refractory (R/R) acute myeloid leukemia (AML). Estimate the maximum tolerated dose (MTD) and / or a biologically optimal dose (eg, recommended phase 2 dose \[RP2D\]).

Conditions

Relapsed/Refractory Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)

  A DLT was any of the following during the DLT window, assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 except for cytokine release syndrome (CRS) grading: * drug-induced liver injury * any treatment-related death * Grade 2 CRS not resolving to ≤ grade 1 within 7 days; grade 3 CRS not resolving to ≤ grade 1 within 7 days; grade 3 CRS reported at the initial run-in dose; 2 separate grade 3 CRS events * Grade 4 CRS/infusion reactions * Grade 3-5 non-hematologic toxicity not clearly resulting from underlying leukemia except: alopecia, grade 3 rash, fatigue, asthenia, fever, anorexia, or constipation, nausea, vomiting or diarrhea not requiring tube feeding, total parenteral nutrition, or requiring/prolonging hospitalization; infection, bleeding, or other expected complication of cytopenias due to underlying leukemia; grade 3 infusion reaction including CRS; grade 3 tumor lysis syndrome * Grade 4 neutropenia persisting beyond 42 days in absence of leukemia.

  Days 1 to 28 for each cohort (28 days)

• Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Treatment-related TEAEs

  An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of investigational product (emirodatamab) up to 30 days after the end of investigational product or end of study date, whichever was earlier. A treatment-related AE was any TEAE that per investigator review had a reasonable possibility of being caused by the investigational product (emirodatamab).

  Day 1 Cycle 1 to 30 days after last dose of investigational product or end of study; median treatment duration was 0.62 months

Secondary Outcomes (8)

• Maximum Observed Concentration (Cmax) of Emirodatamab

  Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: Cycle 1 Day 5 (C1D5); Cohorts 14 and 15: Cycle 1 Day 8 (C1D8) (sampling pre-dose up to 72 hours post-dose)

• Time to Reach Cmax (Tmax) of Emirodatamab

  Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)

• Minimum Concentration (Cmin) of Emirodatamab

  Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)

• Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of Emirodatamab

  Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)

• AUC From Time 0 to Infinity (AUC0-inf) of Emirodatamab

  Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)

Study Arms (2)

Dose Escalation Phase

EXPERIMENTAL

AMG 427 Dose-finding phase of the study

Drug: AMG 427

Dose Expansion Phase

EXPERIMENTAL

AMG 427 MTD identified in dose escalation phase (or lower) will be administered to subjects.

Drug: AMG 427

Interventions

AMG 427 DRUG

AMG 427 will be administered as an intravenous (IV) infusion in adult subjects with relapsed/refractory AML.

Also known as: AMG 427; 20170528

Dose Escalation Phase; Dose 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 greater than or equal to 18 years of age at the time of signing consent.

You may not qualify if:

• Myeloblasts greater than or equal to 5% in bone marrow, as confirmed by immunophenotype by flow cytometry.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2.
• Renal function as follows: serum creatinine less than 2.0 mg/dL (176.84 µmol/L); estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m\^2.
• Hepatic function as follows: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3.0 x upper limit of normal (ULN); bilirubin less than or equal to 1.5 x ULN (unless considered due to Gilbert's syndrome or hemolysis).
• No active tuberculosis in the setting of anti-tumor necrosis factor (TNF) therapy - National guidelines should be followed for the appropriate tuberculosis screening in the setting of anti-TNF therapy, including a minimum of:
• Subject has a negative test for tuberculosis during screening defined as either:
• Negative purified protein derivative (PPD) (\< 5 mm induration at 48 to 72 hours after test is placed) OR
• Negative Quantiferon test
• Subjects with positive PPD and a history of bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test.
• Subjects with a positive PPD test (without a history of bacillus Calmette-Guérin vaccination) or subjects with a positive or indeterminate Quantiferon test are allowed if they have all of the following:
• No symptoms, per tuberculosis worksheet provided by Amgen
• Documented history of a completed course of adequate treatment or prophylaxis (per local standard of care) prior to the start of investigational product
• No known exposure to a case of active tuberculosis after most recent prophylaxis
• No evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product (substudy subjects only)
• Patients with acute promyelocytic leukemia (APML).

Sponsors & Collaborators

• Amgen: lead

Study Sites (16)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

University Health Network-Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Klinikum der Universitaet Muenchen Campus Grosshadern

München, 81377, Germany

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

University of Fukui Hospital

Yoshida-gun, Fukui, 910-1193, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

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

Limitations and Caveats

Due to the early termination of the study, the dose expansion cohort was not opened, and the secondary endpoint for duration of response which was pre-specified for the dose expansion cohort was not collected.

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

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: May 30, 2018
• Study Start: September 14, 2018
• Primary Completion: February 21, 2023
• Study Completion: February 21, 2023
• Last Updated: October 10, 2024
• Results First Posted: October 10, 2024

Record last verified: 2024-07

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

DE (2); US (7); AU (2); CA (1); JP (2); KR (2)