Relapsed/Refractory Acute Myeloid Leukemia (AML)Phase 120170528NCT03541369
Safety, Tolerability, PK, PD, and Efficacy of AMG 427 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing AMG 427 in people with Relapsed/Refractory Acute Myeloid Leukemia (AML), run by Amgen at 16 sites in 6 countries.
Trial summary
Evaluate the safety and tolerability of AMG 427 in adult subjects with relapsed/refractory (R/R) acute myeloid leukemia (AML). Estimate the maximum tolerated dose (MTD) and / or a biologically optimal dose (eg, recommended phase 2 dose [RP2D]). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Acute Myeloid Leukemia (AML)
- What is being tested?
- AMG 427
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 16 sitesin 6 countries
- Study dates
- 14 Sep 2018to 21 Feb 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 µmol/L); estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m^2.
Show all 17Show fewer
- 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-tumor necrosis factor (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)
Who cannot join
- 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 hematopoietic stem cell transplant (HSCT) within 6 weeks prior to start of AMG 427 treatment.
Show all 31Show fewer
- 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 fms-like tyrosine kinase 3 (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)
Trial locations and contacts
16 sites in 6 countries.
16 sites in 6 countries
United States7 sites
Johns Hopkins
Baltimore, Maryland, 21287
Roswell Park Cancer Institute
Buffalo, New York, 14263
City of Hope National Medical Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Northwestern University
Evanston, Illinois, 60208
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Australia2 sites
The Alfred Hospital
Melbourne, Victoria, 3004
The Royal Melbourne Hospital
Parkville, Victoria, 3050
Germany2 sites
Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden
Dresden, 01307
Klinikum der Universitaet Muenchen Campus Grosshadern
München, 81377
Japan2 sites
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
University of Fukui Hospital
Yoshida-gun, Fukui, 910-1193
South Korea2 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital Yonsei University Health System
Seoul, 03722
Canada1 site
University Health Network-Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
About this study
Official title: 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.
Evaluate the safety and tolerability of AMG 427 in adult subjects with relapsed/refractory (R/R) acute myeloid leukemia (AML). Estimate the maximum tolerated dose (MTD) and / or a biologically optimal dose (eg, recommended phase 2 dose [RP2D]).
Read the 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.
- Being tested
- AMG 427
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 427Drug
Also called AMG 427; 20170528
AMG 427 will be administered as an intravenous (IV) infusion in adult subjects with relapsed/refractory AML.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Phase | Experimental | AMG 427 Dose-finding phase of the study Receives: Drug: AMG 427 |
| Dose Expansion Phase | Experimental | AMG 427 MTD identified in dose escalation phase (or lower) will be administered to subjects. Receives: Drug: AMG 427 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
A DLT was any of the following during the DLT window, assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 except for cytokine release syndrome (CRS) grading:
- drug-induced liver injury
- any treatment-related death
- Grade 2 CRS not resolving to ≤ grade 1 within 7 days; grade 3 CRS not resolving to ≤ grade 1 within 7 days; grade 3 CRS reported at the initial run-in dose; 2 separate grade 3 CRS events
- Grade 4 CRS/infusion reactions
- Grade 3-5 non-hematologic toxicity not clearly resulting from underlying leukemia except: alopecia, grade 3 rash, fatigue, asthenia, fever, anorexia, or constipation, nausea, vomiting or diarrhea not requiring tube feeding, total parenteral nutrition, or requiring/prolonging hospitalization; infection, bleeding, or other expected complication of cytopenias due to underlying leukemia; grade 3 infusion reaction including CRS; grade 3 tumor lysis syndrome
- Grade 4 neutropenia persisting beyond 42 days in absence of leukemia.
Measured: Days 1 to 28 for each cohort (28 days)
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Treatment-related TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant.
A TEAE was an AE that started on or after the first dose of investigational product (emirodatamab) up to 30 days after the end of investigational product or end of study date, whichever was earlier.
A treatment-related AE was any TEAE that per investigator review had a reasonable possibility of being caused by the investigational product (emirodatamab).
Measured: Day 1 Cycle 1 to 30 days after last dose of investigational product or end of study; median treatment duration was 0.62 months
Secondary outcomes (8)
Maximum Observed Concentration (Cmax) of Emirodatamab
Serum concentrations of emirodatamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the LLOQ (0.05 ng/mL) were set to zero before data analysis.
Measured: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: Cycle 1 Day 5 (C1D5); Cohorts 14 and 15: Cycle 1 Day 8 (C1D8) (sampling pre-dose up to 72 hours post-dose)
Time to Reach Cmax (Tmax) of Emirodatamab
Serum concentrations of emirodatamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.05 ng/mL) were set to zero before data analysis.
Measured: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
Minimum Concentration (Cmin) of Emirodatamab
Serum concentrations of emirodatamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.05 ng/mL) were set to zero before data analysis.
Measured: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of Emirodatamab
Serum concentrations of emirodatamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.05 ng/mL) were set to zero before data analysis. AUC(0-last) was calculated using the linear trapezoidal method.
Measured: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
AUC From Time 0 to Infinity (AUC0-inf) of Emirodatamab
Serum concentrations of emirodatamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.05 ng/mL) were set to zero before data analysis. The AUC(0-inf) was calculated using the linear trapezoidal method.
Measured: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
AUC From Time Zero to 14 Days Post-dose (AUC14d) of Emirodatamab
Serum concentrations of emirodatamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.05 ng/mL) were set to zero before data analysis. AUC(14d) was calculated as the sum of AUC values of all dosing days in cycle 1.
Measured: For all cohorts: from time zero to 14-days following the C1D1 dose (1 cycle= 14 days)
Terminal Half-life (t1/2,z) of Emirodatamab
Serum concentrations of emirodatamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.05 ng/mL) were set to zero before data analysis. t1/2,z was calculated as t1/2,z = ln(2)/λz, where λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase.
Measured: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
Best Overall Response According to Revised International Working Group (IWG) Response Criteria
A response consisted of any of the following, assessed according to the IWG response criteria:
- complete remission (CR): bone marrow (BM) blasts <5%; no blasts with Auer rods; no extramedullary disease; absolute neutrophil count >1.0 x 10^9/L; platelet count > 100 x 10^9/L; independence of red cell transfusions
- CR with incomplete recovery of peripheral blood counts (CRi): CR except for residual neutropenia (< 1.0 x 10^9/L) or thrombocytopenia (< 100 x 10^9/L)
- complete response/remission with partial hematologic recovery (CRh): ≤5% BM blasts, no circulating blasts/extramedullary disease and partial recovery of peripheral blood counts (platelets > 50,000/µL, hemoglobin ≥7g/dL and absolute neutrophil count > 500/µL).
- morphologic leukemia-free state: BM blasts < 5%; no blasts with Auer rods; no extramedullary disease; no hematologic recovery required
- partial remission: hematological criteria of CR; decrease BM blast to 5-25%; decrease of pretreatment BM blast percentage by ≤ 50%
Measured: Day 1 Cycle 1 to 30 days after last dose of investigational product or end of study; median treatment duration was 0.62 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start14 Sep 2018
- Primary completion21 Feb 2023
- Study completion21 Feb 2023
Why it stopped: Premature discontinuation of study, a strategic decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed/Refractory Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03541369
- Sponsor's protocol ID
- 20170528
- Other IDs
- BB-IND 138440, 2018-001389-40, 2018
- Acronym
- 20170528
- Status last verified
- Jul 2024
- First submitted
- 18 May 2018
- Last updated
- 10 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT03541369
- Acronym / sponsor ID
- 20170528 / 20170528
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Premature discontinuation of study, a strategic decision.
- Enrolment
- 64 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 14 Sep 2018 (actual)
- Primary completion
- 21 Feb 2023 (actual)
- Study completion
- 21 Feb 2023 (actual)
- First posted
- 30 May 2018 (actual)
- Results
- Posted 10 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate the safety and tolerability of AMG 427 in adult subjects with relapsed/refractory (R/R) acute myeloid leukemia (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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Phase | Experimental | Drug: AMG 427AMG 427 Dose-finding phase of the study |
| Dose Expansion Phase | Experimental | Drug: AMG 427AMG 427 MTD identified in dose escalation phase (or lower) will be administered to subjects. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 427Also: AMG 427; 20170528AMG 427 will be administered as an intravenous (IV) infusion in adult subjects with relapsed/refractory AML. | Drug | Dose Escalation Phase, Dose Expansion Phase |
Primary outcome
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
Time frame: Days 1 to 28 for each cohort (28 days)
A DLT was any of the following during the DLT window, assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 except for cytokine release syndrome (CRS) grading: * drug-induced liver injury * any treatment-related death * Grade 2 CRS not resolving to ≤ grade 1 within 7 days; grade 3 CRS not resolving to ≤ grade 1 within 7 days; grade 3 CRS reported at the initial run-in dose; 2 separate grade 3 CRS events * Grade 4 CRS/infusion reactions * Grade 3-5 non-hematologic toxicity not clearly resulting from underlying leukemia except: alopecia, grade 3 rash, fatigue, asthenia, fever, anorexia, or constipation, nausea, vomiting or diarrhea not requiring tube feeding, total parenteral nutrition, or requiring/prolonging hospitalization; infection, bleeding, or other expected complication of cytopenias due to underlying leukemia; grade 3 infusion reaction including CRS; grade 3 tumor lysis syndrome * Grade 4 neutropenia persisting beyond 42 days in absence of leukemia.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Treatment-related TEAEs
Time frame: Day 1 Cycle 1 to 30 days after last dose of investigational product or end of study; median treatment duration was 0.62 months
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of investigational product (emirodatamab) up to 30 days after the end of investigational product or end of study date, whichever was earlier. A treatment-related AE was any TEAE that per investigator review had a reasonable possibility of being caused by the investigational product (emirodatamab).
8 secondary outcomes
Maximum Observed Concentration (Cmax) of Emirodatamab
Time frame: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: Cycle 1 Day 5 (C1D5); Cohorts 14 and 15: Cycle 1 Day 8 (C1D8) (sampling pre-dose up to 72 hours post-dose)
Time to Reach Cmax (Tmax) of Emirodatamab
Time frame: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
Minimum Concentration (Cmin) of Emirodatamab
Time frame: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of Emirodatamab
Time frame: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
AUC From Time 0 to Infinity (AUC0-inf) of Emirodatamab
Time frame: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
AUC From Time Zero to 14 Days Post-dose (AUC14d) of Emirodatamab
Time frame: For all cohorts: from time zero to 14-days following the C1D1 dose (1 cycle= 14 days)
Terminal Half-life (t1/2,z) of Emirodatamab
Time frame: Cohorts 1, 2, 3, 4, 5, 6, 7a, 7b, 8, 9, 10, 11, 12, 13, 16 and 17: C1D5; Cohorts 14 and 15: C1D8 (sampling pre-dose up to 72 hours post-dose)
Best Overall Response According to Revised International Working Group (IWG) Response Criteria
Time frame: Day 1 Cycle 1 to 30 days after last dose of investigational product or end of study; median treatment duration was 0.62 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Related trials for Relapsed/Refractory Acute Myeloid Leukemia (AML)
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
Active, not recruitingPhase 3
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
Acute Myeloid Leukemia
RecruitingPhase 1
First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS)
R/R AML, R/R HR-MDS
RecruitingPhase 2
Olutasidenib in Relapsed IDH1 Mutated AML Patients Who Have Previously Received Venetoclax
IDH1 Mutation, Relapsed / Refractory AML
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
16 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 427 in people with Relapsed/Refractory Acute Myeloid Leukemia (AML), run by Amgen at 16 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Australia, Germany, Japan, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) (time frame: Days 1 to 28 for each cohort (28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.