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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03224819




Registration number
NCT03224819
Ethics application status
Date submitted
3/07/2017
Date registered
21/07/2017

Titles & IDs
Public title
Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Scientific 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
Secondary ID [1] 0 0
2017-002980-16
Secondary ID [2] 0 0
20160377
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Emerfetamab

Experimental: Dose Escalation - 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.

Experimental: Expansion Phase - 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.


Treatment: Drugs: Emerfetamab
Administered by intravenous (IV) infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-emergent Adverse Events
Timepoint [1] 0 0
From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months.
Primary outcome [2] 0 0
Number of Participants With Dose-limiting Toxicities (DLT)
Timepoint [2] 0 0
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 outcome [1] 0 0
Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab
Timepoint [3] 0 0
Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion.
Secondary outcome [4] 0 0
Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab
Timepoint [4] 0 0
Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Secondary outcome [5] 0 0
Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab
Timepoint [5] 0 0
Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Secondary outcome [6] 0 0
Schedule A: AUC Total for Emerfetamab
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab
Timepoint [7] 0 0
Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Secondary outcome [8] 0 0
Schedule A: Clearance (CL) of Emerfetamab
Timepoint [8] 0 0
Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Secondary outcome [9] 0 0
Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab
Timepoint [9] 0 0
Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Secondary outcome [10] 0 0
Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab
Timepoint [10] 0 0
Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Secondary outcome [11] 0 0
Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab
Timepoint [11] 0 0
Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Secondary outcome [12] 0 0
Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab
Timepoint [12] 0 0
Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Secondary outcome [13] 0 0
Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab
Timepoint [13] 0 0
Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Secondary outcome [14] 0 0
Schedule B: Clearance of Emerfetamab
Timepoint [14] 0 0
Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Secondary outcome [15] 0 0
Response Rate
Timepoint [15] 0 0
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.
Secondary outcome [16] 0 0
Duration of Response
Timepoint [16] 0 0
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.
Secondary outcome [17] 0 0
Time to Response
Timepoint [17] 0 0
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.
Secondary outcome [18] 0 0
Time to Progression
Timepoint [18] 0 0
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.

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/12/2020
Sample size
Target
Accrual to date
Final
46
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [2] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Germany
State/province [5] 0 0
München

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03224819