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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03541369
Other study ID # 20170528
Secondary ID BB-IND 138440201
Status Terminated
Phase Phase 1
First received
Last updated
Start date September 14, 2018
Est. completion date February 28, 2023

Study information

Verified date February 2023
Source Amgen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 64
Est. completion date February 28, 2023
Est. primary completion date February 28, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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. - Prior treatment with a FLT3 targeting chimeric antigen receptor T cell (CAR-T) - 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. - 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)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
AMG 427
AMG 427 will be administered as an intravenous (IV) infusion in adult subjects with relapsed/refractory AML.

Locations

Country Name City State
Australia The Alfred Hospital Melbourne Victoria
Australia The Royal Melbourne Hospital Parkville Victoria
Canada University Health Network-Princess Margaret Cancer Centre Toronto Ontario
Germany Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden Dresden
Germany Klinikum der Universitaet Muenchen Campus Grosshadern Muenchen
Japan National Cancer Center Hospital East Kashiwa-shi Chiba
Japan University of Fukui Hospital Yoshida-gun Fukui
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital Yonsei University Health System Seoul
United States Johns Hopkins Baltimore Maryland
United States Roswell Park Cancer Institute Buffalo New York
United States City of Hope National Medical Center Duarte California
United States Duke University Medical Center Durham North Carolina
United States Northwestern University Evanston Illinois
United States University of Texas MD Anderson Cancer Center Houston Texas
United States Memorial Sloan Kettering Cancer Center New York New York

Sponsors (1)

Lead Sponsor Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Japan,  Korea, Republic of, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of subjects who experience a dose limiting toxicity (DLT) Number of subjects experiencing dose limiting toxicities (DLTs) while on treatment with AMG 427. 14 Months
Primary Subject incidence of treatment-emergent adverse events (TEAEs) Incidence of treatment-emergent adverse events (TEAEs) experienced by subjects while on treatment with AMG 427. 14 Months
Primary Subject incidence of treatment-related adverse events (TRAEs) Incidence of treatment-related emergent adverse events (TEAEs) experienced by subjects while on treatment with AMG 427. 14 Months
Secondary Maximum observed concentration (Cmax) of AMG 427 14 months
Secondary Minimum concentration (Cmin) of AMG 427 14 months
Secondary Area under the concentration-time curve (AUC) of AMG 427 14 months
Secondary Half Life (t1/2) of AMG 427 14 months
Secondary Complete response/remission [CR] 14 months
Secondary Complete response/remission with incomplete recovery of peripheral blood counts [CRi] 14 months
Secondary Partial remission (per modified International Working Group IWG criteria) 14 months
Secondary Morphologic leukemia-free state 14 months
Secondary Complete remission with partial hematologic recovery (CRh) 14 months
Secondary Duration of response 14 months
See also
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Not yet recruiting NCT05662904 - Genetic Ablation of CD33 in HSC to Broaden the Therapeutic Index of CD33-directed Immunotherapy in Patients With AML Phase 1
Recruiting NCT06049667 - A Phase 1 Clinical Trail of NTQ2494 Tablets in Patients With Advanced Hematological Malignancies Phase 1