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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03224819
Ethics application status
Date submitted
3/07/2017
Date registered
21/07/2017
Date last updated
20/11/2019

Titles & IDs
Public title
Study of AMG 673 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
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
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 - AMG 673

Experimental: Exploration Phase - Dose finding phase of the study

Experimental: Expansion Phase - Maximum Tolerated Dose identified by Exploration Phase administered to subjects


Treatment: Drugs: AMG 673
Open label.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Subject incidence and grade of adverse events
Timepoint [1] 0 0
18 months
Primary outcome [2] 0 0
Dose limiting toxicities (DLTs)
Timepoint [2] 0 0
18 Months
Secondary outcome [1] 0 0
Pharmacokinetic parameter - half-life
Timepoint [1] 0 0
18 months
Secondary outcome [2] 0 0
Pharmacokinetic parameter - steady state
Timepoint [2] 0 0
18 months
Secondary outcome [3] 0 0
Pharmacokinetic parameter - Concentration
Timepoint [3] 0 0
18 months
Secondary outcome [4] 0 0
Pharmacokinetic parameter - Volume of distribution
Timepoint [4] 0 0
18 months
Secondary outcome [5] 0 0
Pharmacokinetic parameter - Clearance of AMG 673
Timepoint [5] 0 0
18 months
Secondary outcome [6] 0 0
Efficacy parameters - response rate
Timepoint [6] 0 0
18 months
Secondary outcome [7] 0 0
Efficacy parameters - duration of response
Timepoint [7] 0 0
18 months
Secondary outcome [8] 0 0
Efficacy parameters - time to progression
Timepoint [8] 0 0
18 months
Secondary outcome [9] 0 0
Efficacy parameters - time to response
Timepoint [9] 0 0
18 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 WHO Classification (Appendix D) 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, Appendix F) Performance Status of = 2.

- Renal function as follows: serum creatinine < 2.0 mg/dL (176.84 mmol/L) and estimated
glomerular filtration rate > 30 mL/min/1.73 m2.

- Hepatic function as follows: Aspartate aminotransferase (AST) and Alanine
aminotransferase (ALT) = 3.0 x upper limit of normal (ULN). Bilirubin = 1.5 x ULN
(unless considered due to Gilbert's syndrome or hemolysis)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

- Active extramedullary AML in the central nervous system (CNS).

- Known hypersensitivity to immunoglobulins.

- White blood cells (WBC) > 15,000 cells/mcL (15 cells x 10^9/L) at screening. In
subjects with WBC > 15,000 cells/mcL at screening with lymphocyte predominance,
subject may be deemed eligible for the trial by the Amgen physician, after discussion
with the investigator.

- Prior malignancy (other than in situ cancer) unless treated with curative intent and
without evidence of disease for > 2years before screening.

- Autologous 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.

- History or evidence of cardiovascular risk including any of the following:

- History or evidence of clinically significant arrhythmias (ventricular
fibrillation, ventricular tachycardia, supraventricular tachycardia, atrial
tachycardia/flutter, atrial fibrillation with rapid ventricular response, second
or third degree atrioventricular block, and sick sinus syndrome).

- Exception: Subjects with controlled atrial fibrillation for > 30 days prior to
study day 1 are eligible. Controlled atrial fibrillation is defined as atrial
fibrillation with no rapid ventricular response which requires no change in
medication/dosage or addition of new medication or hospital admission within 30
days prior to study day 1.

- History of acute coronary syndromes (eg, myocardial infarction and unstable
angina) and/or coronary angioplasty within 6 months prior to study day 1.

- History or evidence of = Class II congestive heart failure as defined by New York
Heart Association (NYHA).

- Chronic hypertension (defined as a systolic blood pressure [SBP] >140 mm Hg
and/or diastolic blood pressure [DBP] > 90 mm Hg which cannot be controlled by
anti hypertensive therapy).

- Subjects with intra-cardiac defibrillators.

- Abnormal cardiac valve morphology (= grade 2) (subjects with grade 1
abnormalities [ie, mild regurgitation/stenosis] can be entered on study. Subjects
with moderate valvular thickening should not be entered on study).

- History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 3
months.

- Active infection requiring intravenous antibiotics within 1 week of study enrollment
(day 1).

- Known positive test for human immunodeficiency virus (HIV).

- Positive for hepatitis B surface antigen.

- Positive for hepatitis C or chronic hepatitis C.

· Possible exceptions: acute hepatitis C and completely cleared of the virus
(demonstrated by negative viral load), chronic hepatitis C with undetectable viral
load defined by sustained virologic response 24 weeks (SVR24) after completion of
anti-hepatitis C treatment.

- Unresolved toxicities from prior antitumor therapy, defined as not having resolved to
CTCAE, version 4.0 grade 1 (with the exception of myelosuppression, eg, neutropenia,
anemia, thrombocytopenia), or to levels dictated in the eligibilitycriteria with the
exception of alopecia or toxicities from prior antitumor therapy that are considered
irreversible (defined as having been present and stable for > 2 months) which may be
allowed if they are not otherwise described in the exclusion criteria AND there is
agreement to allow by both the investigator and sponsor.

- Antitumor therapy (chemotherapy, antibody therapy, investigational agents,
molecular-targeted therapy or retinoid therapy) within 14 days of day 1. Exception:
hydroxyurea to control peripheral blood leukemic cell counts isallowed until start of
IP treatment.

- Treatment with systemic immune modulators including, but not limited to, non-topical
systemic corticosteroids (exception: physiological replacement and pre-medication for
blood products are permitted), cyclosporine, and tacrolimus within 2 weeks before
enrollment (day 1).

- Prior treatment with chimeric antigen receptor T cell (CAR-T) infusion for the
treatment of AML (CD33 target)

- Major surgery within 28 days of study day 1 with the exception of biopsy and insertion
of central venous catheter.

- History or evidence of any other clinically significant disorder, condition or disease
that, in the opinion of the investigator or Amgen physician, if consulted, would pose
a risk to subject safety or interfere with the study evaluation, procedures or
completion.

- 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.

- Subject likely to not be available to complete all protocol-required study visits or
procedures, and/or to comply with all required study procedures to the best of the
subject and investigator's knowledge.

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
Single group
Other design features
Phase
Phase 0
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment hospital [2] 0 0
Research Site - 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
This is a first-in-human, open-label, phase 1, sequential dose escalation study. AMG 673 will
be evaluated as a short term intravenous (IV) infusion in adult subjects with
relapsed/refractory AML. The study will be conducted at approximately 7 sites in the United
States, Australia and Germany.
Trial website
https://clinicaltrials.gov/show/NCT03224819
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
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03224819