Clinical Trials /

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

NCT03224819

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AMG 673 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 20160377
  • NCT ID: NCT03224819

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
AMG 673Expansion Phase

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Exploration PhaseExperimentalDose finding phase of the study
  • AMG 673
Expansion PhaseExperimentalMaximum Tolerated Dose identified by Exploration Phase administered to subjects
  • AMG 673

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Subject incidence and grade of adverse events
Time Frame:18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic parameter - half-life
Time Frame:18 months
Safety Issue:
Description:
Measure:Pharmacokinetic parameter - steady state
Time Frame:18 months
Safety Issue:
Description:
Measure:Pharmacokinetic parameter - Concentration
Time Frame:18 months
Safety Issue:
Description:
Measure:Pharmacokinetic parameter - Volume of distribution
Time Frame:18 months
Safety Issue:
Description:
Measure:Pharmacokinetic parameter - Clearance of AMG 673
Time Frame:18 months
Safety Issue:
Description:
Measure:Efficacy parameters - response rate
Time Frame:18 months
Safety Issue:
Description:
Measure:Efficacy parameters - duration of response
Time Frame:18 months
Safety Issue:
Description:
Measure:Efficacy parameters - time to progression
Time Frame:18 months
Safety Issue:
Description:
Measure:Efficacy parameters - time to response
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Last Updated

November 19, 2019