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Safety, Tolerability, PK, PD, and Efficacy of AMG 427 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (20170528)

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: NCT03541369
Recruitment Status : Recruiting
First Posted : May 30, 2018
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE May 18, 2018
First Posted Date  ICMJE May 30, 2018
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE September 14, 2018
Estimated Primary Completion Date December 19, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2019)
  • Subject incidence of dose limiting toxicities (DLTs) [ Time Frame: 14 Months ]
    Incidence of dose-limiting toxicities (DLTs) experienced by subjects while on treatment with AMG 427.
  • Subject incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: 14 Months ]
    Incidence of treatment-emergent adverse events (TEAEs) experienced by subjects while on treatment with AMG 427.
  • Subject incidence of treatment-related adverse events (TRAEs) [ Time Frame: 14 Months ]
    Incidence of treatment-related emergent adverse events (TEAEs) experienced by subjects while on treatment with AMG 427.
Original Primary Outcome Measures  ICMJE
 (submitted: May 18, 2018)
  • Subject incidence of dose limiting toxicities (DLTs) [ Time Frame: 14 Months ]
  • Subject incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: 14 Months ]
  • Subject incidence of treatment-related adverse events (TRAEs) [ Time Frame: 14 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2019)
  • Maximum observed concentration (Cmax) of AMG 427 [ Time Frame: 14 months ]
  • Minimum concentration (Cmin) of AMG 427 [ Time Frame: 14 months ]
  • Area under the concentration-time curve (AUC) of AMG 427 [ Time Frame: 14 months ]
  • Half Life (t1/2) of AMG 427 [ Time Frame: 14 months ]
  • Complete response/remission [CR] [ Time Frame: 14 months ]
  • Complete response/remission with incomplete recovery of peripheral blood counts [CRi] [ Time Frame: 14 months ]
  • Partial remission (per modified International Working Group IWG criteria) [ Time Frame: 14 months ]
  • Morphologic leukemia-free state [ Time Frame: 14 months ]
  • Complete remission with partial hematologic recovery (CRh) [ Time Frame: 14 months ]
  • Duration of response [ Time Frame: 14 months ]
  • Relapse free survival [ Time Frame: 14 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, PK, PD, and Efficacy of AMG 427 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 427 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia.
Brief Summary Evaluate the safety and tolerability of AMG 427 in adult subjects with relapsed/refractory AML. Estimate the maximum tolerated dose (MTD) and / or a biologically optimal dose (eg, recommended phase 2 dose [RP2D]).
Detailed Description Evaluate the safety and tolerability of AMG 427 in adult subjects with relapsed/refractory AML. Estimate the maximum tolerated dose (MTD) and / or a biologically optimal dose (eg, recommended phase 2 dose [RP2D]). Approximately 80 subjects will be enrolled.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed/Refractory Acute Myeloid Leukemia (AML)
Intervention  ICMJE Drug: AMG 427
AMG 427 will be administered as an intravenous (IV) infusion in adult subjects with relapsed/refractory AML.
Other Name: AMG 427; 20170528
Study Arms  ICMJE
  • Experimental: Dose Escalation Phase
    AMG 427 Dose-finding phase of the study
    Intervention: Drug: AMG 427
  • Experimental: Dose Expansion Phase
    AMG 427 MTD identified in dose escalation phase (or lower) will be administered to subjects.
    Intervention: Drug: AMG 427
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: May 18, 2020)
105
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2018)
70
Estimated Study Completion Date  ICMJE December 19, 2022
Estimated Primary Completion Date December 19, 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 greater than or equal to 18 years of age at the time of signing consent.
  • AML as defined by the WHO Classification as persisting or recurring following 1 or more treatment courses (exceptions noted in exclusión criteria).
  • Myeloblasts greater than or equal to 5% in bone marrow, as confirmed by immunophenotype by flow cytometry.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2.
  • Renal function as follows: serum creatinine greater than 2.0 mg/dL (176.84 mol/L); estimated glomerular filtration rate (eGFR) less tan 30 mL/min/1.73 m2.
  • Hepatic function as follows: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3.0 x upper limit of normal (ULN); bilirubin less than or equal to 1.5 x ULN (unless considered due to Gilbert's syndrome or hemolysis).
  • No active tuberculosis in the setting of anti-TNF therapy - National guidelines should be followed for the appropriate tuberculosis screening in the setting of anti-TNF therapy, including a minimum of:

    • Subject has a negative test for tuberculosis during screening defined as either:

      • Negative purified protein derivative (PPD) (< 5 mm induration at 48 to 72 hours after test is placed) OR
      • Negative quantiferon test
    • Subjects with positive PPD and a history of bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test.
    • Subjects with a positive PPD test (without a history of bacillus Calmette-Guérin vaccination) or subjects with a positive or indeterminate Quantiferon test are allowed if they have all of the following:

      • no symptoms, per tuberculosis worksheet provided by Amgen
      • documented history of a completed course of adequate treatment or prophylaxis (per local standard of care) prior to the start of investigational product
      • no known exposure to a case of active tuberculosis after most recent prophylaxis
      • no evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product (substudy subjects only)

Exclusion Criteria:

  • Patients with acute promyelocytic leukemia (APML).
  • Active extramedullary AML in the central nervous system (CNS)
  • Known hypersensitivity to immunoglobulins.
  • White blood cells (WBC) greater than 15,000 cells/mcL (15 cells x 10^9/L) at screening (hydroxyurea is permitted to enable eligibility).
  • Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for greater than 2 years before screening.
  • Autologous HSCT within 6 weeks prior to start of AMG 427 treatment.
  • Allogeneic HSCT within 3 months prior to start of AMG 427 treatment.
  • Any graft-versus-host disease requiring systemic therapy with immunomodulators.
  • History or evidence of significant cardiovascular risk including any of the following: symptomatic congestive heart failure, unstable angina, clinically significant arrhythmias (eg, ventricular fibrillation, ventricular tachycardia etc.), recent coronary angioplasty, intra-cardiac defibrillators or any clinically relevant concurrent disorder that may pose a risk to subject safety or interfere with study evaluation, procedures, or completion.
  • 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). Antibiotics may be administered for prophylaxis as per institutional standards up to and after enrollment.
  • Known positive test for human immunodeficiency virus (HIV).
  • Positive for hepatitis B surface antigen (HepBsAg).
  • 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.
  • Live vaccination(s) within 4 weeks before the start of AMG 427 treatment on day 1, during treatment, and until the end of the last study dose.
  • Unresolved toxicities from prior antitumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 grade 1 (with the exception of myelosuppression, eg, neutropenia, anemia, thrombocytopenia), or to levels dictated in the eligibility criteria with the exception of alopecia or toxicities from prior antitumor therapy that are considered irreversible (defined as having been present and stable for greater than 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, molecular-targeted therapy, or investigational agent) within 14 days of day 1. Exception: hydroxyurea to control peripheral blood leukemic cell counts is allowed until start of investigational product treatment.
  • Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids, cyclosporine, and tacrolimus within 2 weeks before enrollment (day 1). Exceptions: physiologic replacement steroids or steroids for treatment of transfusion/hypersensitivity reactions.
  • 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 medical monitor 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 4 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).
  • Females who are lactating/breastfeeding or who plan to breastfeed while on study through 4 weeks after receiving the last dose of study drug.
  • Females with a positive pregnancy test.
  • Females planning to become pregnant while on study through 4 weeks after receiving the last dose of study drug.
  • Subjects 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's and investigator's knowledge.
  • History of multiple sclerosis or any other demyelinating disease.
  • No active hepatitis secondary to alcoholic hepatitis or nonalcoholic steatohepatitis.
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,   Canada,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03541369
Other Study ID Numbers  ICMJE 20170528
BB-IND 138440 ( Other Grant/Funding Number: IND Number )
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 URL 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 October 2020

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