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

  • STATUS
    Recruiting
  • End date
    May 5, 2027
  • participants needed
    200
  • sponsor
    Amgen
Updated on 10 July 2022

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]).

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.

Details
Condition Relapsed/Refractory Acute Myeloid Leukemia (AML)
Treatment AMG 427
Clinical Study IdentifierNCT03541369
SponsorAmgen
Last Modified on10 July 2022

Eligibility

Yes No Not Sure

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
For relapsed/refractory AML subjects only, AML as defined by the WHO Classification as persisting or recurring following 1 or more treatment courses (exceptions noted in exclusion 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 less than 2.0 mg/dL (176.84 mol/L); estimated glomerular filtration rate (eGFR) greater than 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)
Subjects with a prior or concurrent malignancy whose natural history or treatment is anticipated to interfere with the safety or efficacy assessment of the investigational regimen. Exception: Subjects with prior or concurrent malignancy not anticipated to interfere with the safety or efficacy of the investigational regimen may be included only after discussion with the Amgen Medical Monitor
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. Exception: antitumor therapies with short half-lives only require passing of 5 half-lives from last dose, and after discussion with sponsor
Treatment with systemic immune modulators including, but not limited to, non-topical 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
Prior treatment with a FLT3 targeting chimeric antigen receptor T cell (CAR-T)
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
History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with Medical Monitor and meeting the following criteria
Negative test for SARS-CoV-2 RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) within 72 hours of first dose of investigational product
No acute symptoms of coronavirus disease 2019 (COVID-19) disease within 10 days prior to first dose of investigational product (counted from day of positive test for asymptomatic subjects)
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