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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03465540




Registration number
NCT03465540
Ethics application status
Date submitted
8/03/2018
Date registered
14/03/2018
Date last updated
16/06/2020

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Multiple Myeloma, NHL, and AML
Scientific title
A Phase 1 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies
Secondary ID [1] 0 0
20170173
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Non-Hodgkin's Lymphoma 0 0
Acute Myeloid Leukemia 0 0
AML 0 0
NHL 0 0
DLBCL 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
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 397

Experimental: AMG 397 Treatment - AMG 397 administered orally once daily for 2 consecutive days followed by 5 days break at a weekly interval, as part of a 28-day treatment cycle in adult subjects with selected RR hematological malignancies


Treatment: Drugs: AMG 397
potent and selective inhibitor of protein-protein interactions between myeloid cell leukemia sequence 1 and pro-apoptotic members of the lymphoma/leukemia 2 family

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

Outcomes
Primary outcome [1] 0 0
Subject incidence of dose limiting toxicity - Number of dose limiting toxicity
Timepoint [1] 0 0
Up to 3 years
Primary outcome [2] 0 0
Incidence of treatment-emergent adverse events, treatment-related adverse events - Number of adverse events
Timepoint [2] 0 0
Up to 3 years
Primary outcome [3] 0 0
Incidence of Clinically-significant changes in vital signs - Number of changes in vital signs
Timepoint [3] 0 0
Up to 3 years
Primary outcome [4] 0 0
Incidence of Clinically significant changes in ECGs - Number of changes in ECGs
Timepoint [4] 0 0
Up to 3 years
Primary outcome [5] 0 0
Incidence of clinically-significant changes in physical examinations - Number of changes in physical examinations
Timepoint [5] 0 0
Up to 3 years
Primary outcome [6] 0 0
Incidence of Clinically significant changes in clinical laboratory tests - Number of changes in clinical laboratory tests
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Objective response rate (ORR) - Objective response rate (ORR)
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Duration of response - Duration of response
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Progression-free survival (PFS) - Progression-free survival (PFS)
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Overall survival (OS) - Overall survival (OS)
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
AMG 397 PK parameter of maximum observed concentration - AMG 397 PK parameter of maximum observed concentration
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
PK parameter of time of maximum observed concentration (tmax) - PK parameter of time of maximum observed concentration (tmax)
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
PK parameter of area under the concentration time curve (AUC) - PK parameter of area under the concentration time curve (AUC)
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
PK parameter of clearance (CL) - PK parameter of clearance (CL)
Timepoint [8] 0 0
Up to 3 years
Secondary outcome [9] 0 0
PK parameter of half-life (t1/2) - PK parameter of half-life (t1/2)
Timepoint [9] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
- Subject has provided informed consent prior to initiation of any study-specific
activities/procedures

- Age = 18 years old

- Pathologically-documented, definitively-diagnosed relapsed or refractory MM, NHL, or
AML and is intolerant to, or considered ineligible for available therapies known to
provide clinical benefit.

- MM subjects only: Measurable disease per the IMWG response criteria, as indicated by
one or more of the following: Serum M-protein = 0.5 g/dL, Urine M-protein = 200 mg/24
hours. For Subjects who do not meet 1 of the 2 prior criteria: Serum Free Light Chain
(sFLC) = 10 mg/dL (= 100 mg/L) and an abnormal sFLC ratio (< 0.26 or > 1.65) as per
the IMWG response criteria

- NHL subjects only: Radiographically measurable disease with a clearly demarcated nodal
lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least
1.0 cm in its largest dimension

- AML subjects only: Pathologically confirmed diagnosis of AML as defined by the WHO
Classification, More than 5% blasts in bone marrow

- Eastern Cooperative Oncology Group (ECOG) performance status of = 2

- MM and NHL subjects only:

. Hematological function, as follows without transfusion or growth factor support
within 2 weeks prior to study day 1:

- Absolute neutrophil count . 1.0 X 109/L

- Hemoglobin &gt; 8 g/dL

- Platelet count . 75 X 109/L Note: for MM subjects only: Platelet count . = 50 X
109/L (in subjects where &lt; 50% of bone marrow nucleated cells were plasma
cells) OR = 30 X 109/L (in subjects where =50% of bone marrow nucleated cells
were plasma cells) without transfusion or growth factor support are allowed into
the study

- Able to swallow and retain orally administered medication and does not have any
clinically significant gastrointestinal abnormalities that may alter absorption

- Hepatic function, as follows: Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 3 x upper limit of normal (ULN), Total bilirubin (TBIL) < 1.5
X ULN (except subjects with Gilbert's syndrome)

- Cardiac function, as follows: Cardiac ejection fraction = 50% and no evidence of
pericardial effusion as determined by an ECHO or MUGA, No clinically significant ECG
findings.

- Renal function as follows: Calculated or measured creatinine clearance (CrCl) of = 30
mL/minute calculated using the formula of Cockcroft and Gault [(140 - Age) × Mass (kg)
/ (72 × serum creatinine mg/dL)]. Multiply result by 0.85 if female.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previously received an allogeneic stem cell transplant within 6 months of study day 1
OR having signs or symptoms of acute or chronic graft-versus-host disease

- Autologous stem cell transplant < 90 days prior to study day 1

- Candidates for stem cell transplant should have failed or are not considered eligible
for either allogeneic and autologous transplant

- Myocardial infarction within 6 months of study day 1

- Symptomatic congestive heart failure (New York Heart Association > Class II)

- History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 6
months prior to study day 1

- Infection requiring intravenous anti-infective treatments within 1 week of study day 1

- Known positive results for human immunodeficiency virus (HIV)

- Active hepatitis B and C based on the following results: Positive for hepatitis B
surface antigen (HBsAg) (indicative of chronic, hepatitis B or recent acute hepatitis
B), Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA
by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA
suggests occult hepatitis B. Positive Hepatitis C virus antibody (HCVAb): hepatitis C
virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic
hepatitis C

- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to
Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1, or to
levels dictated in the eligibility criteria with the exception of grade 2peripheral
neuropathy, alopecia or toxicities from prior anti-tumor therapy that are considered
irreversible (defined as having been present and stable for > 4 weeks prior to study
day 1 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, molecular-targeted therapy,
retinoid therapy, or investigational agent or procedures) within 14 days of day 1

- Prior systemic radiation therapy must have been completed at least 28 days before
study day 1. Prior focal radiotherapy completed at 14 days before study day 1

- Males and females of reproductive potential who are unwilling to practice an
acceptable method(s) of effective birth control while on study through 3 months after
receiving the last dose of study drug. Acceptable methods of effective birth control
include sexual abstinence (males, females); vasectomy; bilateral tubal
ligation/occlusion; or a condom with spermicide (men) in combination with barrier
methods (diaphragm, cervical cap, or cervical sponge), hormonal birth control or IUD
(females)

- Females who are lactating/breastfeeding or who plan to breastfeed while on study
through 3 months after receiving the last dose of study drug

- Females with a positive pregnancy test or planning to become pregnant while on study
through 3 months after receiving the last dose of study drug

- Males who are unwilling to abstain from sperm donation while on study through 3 months
after receiving the last dose of study drug

- History of other malignancy except:

- Malignancy treated with curative intent and with no known active disease present
for . 2 years before enrollment and felt to be at low risk for recurrence by the
treating physician

- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease

- Adequately treated cervical carcinoma in situ without evidence of disease

- Adequately treated breast ductal carcinoma in situ without evidence of disease

- Prostatic intraepithelial neoplasia without evidence of prostate cancer

- Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ

- 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.

- Use of any over-the-counter or prescription medications within 14 days or 5 half-lives
(whichever is longer), prior to study day 1 that was not reviewed and approved by the
principal investigator and the Amgen medical monitor.

- Use of herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by
the subject within 14 days prior to study day 1 that was not reviewed and approved by
the principal investigator and the Amgen medical monitor

- Use of any known inhibitors of P-gp within 14 days or 5 half-lives (whichever is
longer) or grapefruit juice or grapefruit containing products within 7 days prior to
study day 1 that was not reviewed and approved by the principal investigator and the
Amgen medical monitor.

- Use of known cytochrome P450 (CYP) 3A4 sensitive substrates, (with a narrow
therapeutic window), within 14 days or 5 half-lives (whichever is longer) of the drug
or its major active metabolite, whichever is longer, prior to study day 1 that was not
reviewed and approved by the principal investigator and the Amgen medical monitor.

- Use of known P-gp substrates (with a narrow therapeutic window) within 14 days or 5
half-lives (whichever is longer) prior to study day 1 that was not reviewed and
approved by the principal investigator and the Amgen medical monitor

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

- Known sensitivity to any of the products or component to be administered during dosing

- MM subjects with any of the following criteria are excluded:

- Multiple myeloma with IgM subtype

- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,
and skin changes)

- Existing plasma cell leukemia

- Waldenstrom's macroglobulinemia

- Amyloidosis

- NHL subjects with the following criteria are excluded:

- CNS lymphoma or evidence of uncontrolled CNS disease

- Burkitt's lymphoma

- Lymphoblastic lymphoma

- AML subjects with any of the following criteria are excluded:

- Circulating white blood cells &gt; 25,000 /µl. Hydroxyurea to control peripheral
blood leukemic cell counts, within 24 hours of study day 1 is permitted.

- Promyelocitic leukemia

Study design
Purpose of the study
Treatment
Allocation to intervention
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 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Woolloongabba
Recruitment hospital [3] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
France
State/province [12] 0 0
Marseille Cedex 09
Country [13] 0 0
France
State/province [13] 0 0
Villejuif
Country [14] 0 0
Greece
State/province [14] 0 0
Athens
Country [15] 0 0
Italy
State/province [15] 0 0
Bergamo
Country [16] 0 0
Italy
State/province [16] 0 0
Bologna
Country [17] 0 0
Japan
State/province [17] 0 0
Gifu

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

Ethics approval
Ethics application status

Summary
Brief summary
Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs)
and/or biologically active doses.
Trial website
https://clinicaltrials.gov/show/NCT03465540
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

Summary results
Other publications