Clinical trial NCT03224819: Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Official title: A Phase 1 First-In-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 673 Administered as Short Term Intravenous Infusions in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Acute Myeloid Leukemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-07-21
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Bayesian Model
Primary purpose: TREATMENT

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 \[RP2D\]).

Detailed description: This is a first-in-human, open-label, phase 1, sequential dose escalation study. Emerfetamab will be evaluated as a short term intravenous (IV) infusion in adults with relapsed/refractory AML The study will consist of a dose escalation phase and a dose expansion phase. The study was terminated prior to the start of the expansion phase.

Eligibility criteria: Inclusion Criteria

* 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.

Exclusion Criteria

* 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months.
measure: Number of Participants With Dose-limiting Toxicities (DLT)
timeFrame: 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:
measure: Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab
timeFrame: 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.
measure: Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab
timeFrame: 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.
measure: Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab
timeFrame: Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion.
measure: Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab
timeFrame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
measure: Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab
timeFrame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
measure: Schedule A: AUC Total for Emerfetamab
timeFrame: 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.
measure: Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab
timeFrame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
measure: Schedule A: Clearance (CL) of Emerfetamab
timeFrame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
measure: Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab
timeFrame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
measure: Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab
timeFrame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
measure: Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab
timeFrame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
measure: Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab
timeFrame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
measure: Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab
timeFrame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
measure: Schedule B: Clearance of Emerfetamab
timeFrame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
measure: Response Rate
timeFrame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
measure: Duration of Response
timeFrame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
measure: Time to Response
timeFrame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
measure: Time to Progression
timeFrame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: MÃ¼nchen
country: Germany
facility: Klinikum der Ludwig Maximilians Univeritaet
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: