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Study of AMG 673 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03224819
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : November 20, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE July 3, 2017
First Posted Date  ICMJE July 21, 2017
Last Update Posted Date November 20, 2019
Actual Study Start Date  ICMJE September 7, 2017
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2017)
  • Subject incidence and grade of adverse events [ Time Frame: 18 months ]
  • Dose limiting toxicities (DLTs) [ Time Frame: 18 Months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2019)
  • Pharmacokinetic parameter - half-life [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - steady state [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - Concentration [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - Volume of distribution [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - Clearance of AMG 673 [ Time Frame: 18 months ]
  • Efficacy parameters - response rate [ Time Frame: 18 months ]
  • Efficacy parameters - duration of response [ Time Frame: 18 months ]
  • Efficacy parameters - time to progression [ Time Frame: 18 months ]
  • Efficacy parameters - time to response [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2017)
  • Pharmacokinetic parameter - half-life [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - steady state [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - Concentration [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - Volume of distribution [ Time Frame: 18 months ]
  • Pharmacokinetic parameter - Clearance of AMG 673 [ Time Frame: 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 19, 2017)
  • Efficacy parameters - response rate [ Time Frame: 18 months ]
  • Efficacy parameters - duration of response [ Time Frame: 18 months ]
  • Efficacy parameters - time to progression [ Time Frame: 18 months ]
  • Efficacy parameters - time to response [ Time Frame: 18 months ]
 
Descriptive Information
Brief Title  ICMJE Study of AMG 673 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Bayesian Model
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE Drug: AMG 673
Open label.
Study Arms  ICMJE
  • Experimental: Exploration Phase
    Dose finding phase of the study
    Intervention: Drug: AMG 673
  • Experimental: Expansion Phase
    Maximum Tolerated Dose identified by Exploration Phase administered to subjects
    Intervention: Drug: AMG 673
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 19, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2022
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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) 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Australia,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03224819
Other Study ID Numbers  ICMJE 20160377
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 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.
Access Criteria: 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 link below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP