Clinical Trials /

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

NCT03541369

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]).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, PK, PD, and Efficacy of AMG 427 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 427 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia.

Clinical Trial IDs

  • ORG STUDY ID: 20170528
  • SECONDARY ID: BB-IND 138440
  • NCT ID: NCT03541369

Conditions

  • Relapsed/Refractory Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
AMG 427AMG 427; 20170528Dose Escalation Phase

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation PhaseExperimentalAMG 427 Dose-finding phase of the study
  • AMG 427
Dose Expansion PhaseExperimentalAMG 427 MTD identified in dose escalation phase (or lower) will be administered to subjects.
  • AMG 427

Eligibility Criteria

        Inclusion Criteria:

          -  Subject has provided informed consent prior to initiation of any study-specific
             activities/procedures.

          -  Subjects greater than or equal to18 years of age at the time of signing consent.

          -  AML as defined by the WHO Classification (Appendix D) 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, Appendix F) 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 tan 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).

        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 hydrocortisone for
             treatment of transfusion 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:subject incidence of dose limiting toxicities (DLTs)
Time Frame:14 Months
Safety Issue:
Description:Incidence of dose-limiting toxicities (DLTs) experienced by subjects while on treatment with AMG 427.

Secondary Outcome Measures

Measure:Maximum observed concentration (Cmax) of AMG 427
Time Frame:14 months
Safety Issue:
Description:
Measure:minimum concentration (Cmin) of AMG 427
Time Frame:14 months
Safety Issue:
Description:
Measure:area under the concentration-time curve (AUC) of AMG 427
Time Frame:14 months
Safety Issue:
Description:
Measure:Half Life (t1/2) of AMG 427
Time Frame:14 months
Safety Issue:
Description:
Measure:complete response/remission [CR]
Time Frame:14 months
Safety Issue:
Description:
Measure:complete response/remission with incomplete recovery of peripheral blood counts [CRi]
Time Frame:14 months
Safety Issue:
Description:
Measure:partial remission (per modified International Working Group IWG criteria)
Time Frame:14 months
Safety Issue:
Description:
Measure:morphologic leukemia-free state
Time Frame:14 months
Safety Issue:
Description:
Measure:complete remission with partial hematologic recovery (CRh)
Time Frame:14 months
Safety Issue:
Description:
Measure:duration of response
Time Frame:14 months
Safety Issue:
Description:
Measure:relapse free survival
Time Frame:14 months
Safety Issue:
Description:

Details

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

Last Updated

February 5, 2020