Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies

Stopped early · Phase 1

Conditions studied: Multiple Myeloma, Acute Myeloid Leukemia, Non-Hodgkins Lymphoma, Myelodysplastic Syndrome, AML, MDS, NHL

In brief

Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs) and/or biologically active doses.

Key facts

Study ID

NCT03465540

Run by

Amgen

People needed

24

Starts

2018-08-17

Expected to finish

2019-07-25

Last updated by the study team

2023-04-12

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 multiple myeloma (MM), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) and is intolerant to, or considered ineligible for available therapies known to provide clinical benefit
• MM subjects only: Measurable disease per the International Myeloma Working Group (IMWG) response criteria (assessed within 21 days prior to enrollment), as indicated by one or more of the following: cytogenic risk factor: 1q21 amplification/gain, 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
• MM 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 > 8 g/dL and platelet count ≥ 75 X 109/L
• AML subjects only: Pathologically confirmed diagnosis of AML as defined by the World Health Organisation (WHO) Classification, more than 5% blasts in bone marrow and persisting or recurring following one or more treatment courses
• MDS subjects only: pathologically confirmed diagnosis of MDS as defined by the WHO Classification, intermediate and high risk MDS and intolerant or refractory to HMA treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Life expectancy of > 3 months, based on the opinion of the investigator
• 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 (TBL) < 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 echocardiogram or multigated acquisition (MUGA) scan
• no ECG findings representing a recent cardiac injury within 6 months before enrollment
• 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

You may not qualify if…

• Disease Related
• 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 before enrollment
• Candidates for stem cell transplant should have failed or are not considered eligible for either allogeneic and autologous transplant
• Other Medical Conditions
• 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
• Myocardial infarction within 6 months before enrollment
• 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 before enrollment
• Uncontrollable active infection requiring intravenous anti-infective treatments within 1 week before enrollment
• 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
• Females of reproductive potential who are unwilling to practice acceptable methods of highly effective contraception while on study through 8 months after receiving the last dose of study drug. Males who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use a condom with or without spermicide while on study through 5 months after receiving the last dose of study drug if sexually active with a female of childbearing potential
• Females who are lactating/breastfeeding or who plan to breastfeed while on study through 8 months after receiving the last dose of study drug
• Females with a positive pregnancy test or planning to become pregnant while on study through 8 months after receiving the last dose of study drug
• Males who are unwilling to abstain from sperm donation while on study through 8 months after receiving the last dose of study drug

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States
• Mayo Clinic Arizona — Phoenix, Arizona, United States
• Mayo Clinic Florida — Jacksonville, Florida, United States
• University of Kansas Cancer Center — Westwood, Kansas, United States
• University of Maryland Greenebaum Cancer Center — Baltimore, Maryland, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Mayo Clinic Rochester — Rochester, Minnesota, United States
• Washington University — St Louis, Missouri, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• University of Texas MD Anderson Cancer Center — Houston, Texas, United States
• Froedtert and Med College Wisconsin — Milwaukee, Wisconsin, United States
• Royal Prince Alfred Hospital — Camperdown, New South Wales, Australia
• Princess Alexandra Hospital — Woolloongabba, Queensland, Australia
• The Alfred Hospital — Melbourne, Victoria, Australia
• Institut Paoli Calmettes — Marseille, France
• Institut Gustave Roussy — Villejuif, France
• Alexandra Hospital — Athens, Greece
• Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII — Bergamo, Italy
• Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi — Bologna, Italy
• Ogaki Municipal Hospital — Ogaki-shi, Gifu, Japan

Full record on ClinicalTrials.gov

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