Clinical Trials /

AMG 176 First in Human Trial in Subjects With Relapsed or Refractory Multiple Myeloma and Subjects With Relapsed or Refractory Acute Myeloid Leukemia

NCT02675452

Description:

At least one dose level of AMG 176 will achieve acceptable safety and tolerability in subjects with relapsed or refractory multiple myeloma and subjects with relapsed or refractory acute myeloid leukemia

Related Conditions:
  • Acute Myeloid Leukemia
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AMG 176 First in Human Trial in Subjects With Relapsed or Refractory Multiple Myeloma and Subjects With Relapsed or Refractory Acute Myeloid Leukemia
  • Official Title: A Phase 1 First in Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 176 in Subjects With Relapsed or Refractory Multiple Myeloma and Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 20150161
  • SECONDARY ID: 2015-004777-32
  • NCT ID: NCT02675452

Conditions

  • Relapsed or Refractory Multiple Myeloma
  • Relapsed or Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
AMG 176Study Investigational Product (IP)AMG 176 - Part 1a
AzacitidineAMG 176 - Part 4
ItraconazoleAMG 176 - Part 3d

Purpose

At least one dose level of AMG 176 will achieve acceptable safety and tolerability in subjects with relapsed or refractory multiple myeloma and subjects with relapsed or refractory acute myeloid leukemia

Detailed Description

      This is a Phase 1, first-in-human, multicenter; non-randomized, open-label and
      dose-exploration study of AMG 176 administered IV in subjects with relapsed or refractory
      multiple myeloma and subjects with relapsed or refractory acute myeloid leukemia The study
      will be conducted in four parts.
    

Trial Arms

NameTypeDescriptionInterventions
AMG 176 - Part 1aExperimentalPart 1a - Participants with muliple myeloma (MM) administered AMG 176 as an intravenous (IV) infusion for two-consecutive days (QD2) followed by a 5 days break.
  • AMG 176
AMG 176 - Part 1bExperimentalPart 1b - Participants with multiple myeloma (MM) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break.
  • AMG 176
AMG 176 - Part 3aExperimentalPart 3a - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion once a day, for two-consecutive days (QD2) followed by a 5 day break.
  • AMG 176
AMG 176 - Part 3bExperimentalPart 3b - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break.
  • AMG 176
AMG 176 - Part 3cExperimentalPart 3c - Participants in Japan only with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break.
  • AMG 176
AMG 176 - Part 3dExperimentalPart 3d - Participants in the United States with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW), for 3 weeks, in combination with itraconazole.
  • AMG 176
  • Itraconazole
AMG 176 - Part 4ExperimentalPart 4 - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break, in combination with azacitidine.
  • AMG 176
  • Azacitidine

Eligibility Criteria

        INCLUSION CRITERIA:

          -  For participants in Japan only: if a participant is younger than 20 years at the time
             of signing the informed consent form, informed consent must be obtained from both the
             participant and his/her legal representative

          -  (Multiple myeloma subjects) Pathologically documented, multiple myeloma relapsed or
             refractory disease after at least 2 lines of therapy

          -  (MM subjects only) Measurable disease per the IMWG response criteria

          -  (Acute myeloid leukemia subjects) AML as defined by the World Health Organization
             (WHO) Classification persisting or recurring following one or more treatment courses,
             and for participants in Japan, determined by the investigator to be not eligible for
             approved anticancer drug therapy in Japan; EXCEPT acute promyelocytic leukemia.

          -  (AML subjects only) More than 5% blasts in bone marrow and Circulating white blood
             cells (WBCs) < 25,000/ul.

          -  Must be willing and able to undergo a core bone marrow biopsy (MM subjects only) and
             bone marrow aspirate (MM and AML subjects) at screening.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2,

          -  (MM subjects only) Satisfactory hematological function without transfusion or growth
             factor support

          -  Life expectancy of > 3 months, in the opinion of the investigator

          -  Adequate hepatic function

          -  Adequate cardiac function

          -  Adequate renal function

          -  Female subjects of childbearing potential must have a negative serum or urine
             pregnancy test

          -  Other inclusion criteria may apply

        EXCLUSION CRITERIA:

          -  Previously received an allogeneic stem cell transplant within 6 months OR having
             received immunosuppressive therapy within the last three months OR having signs or
             symptoms of acute or chronic graft-versus-host disease

          -  Autologous stem cell transplant less than 90 days prior to study day 1

          -  (MM subjects only) Multiple myeloma with IgM subtype

          -  (MM subjects only) POEMS syndrome

          -  (MM subjects only) Existing plasma cell leukemia

          -  (MM subjects only) Waldenstrom's macroglobulinemia

          -  (MM subjects only) Amyloidosis

          -  (Acute myeloid leukemia Part 4 only) Presence of advanced malignant hepatic tumors
             with baseline albumin < 3 g/dL

          -  Infection requiring intravenous anti-infective treatments within 1 week of study
             enrollment (day 1)

          -  Myocardial infarction within 6 months of enrollment, symptomatic congestive heart
             failure (New York Heart Association > class II)

          -  History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 6
             months prior to enrollment

          -  Currently receiving treatment in another investigational device or drug study. Other
             investigational procedures while participating in this study will be allowed if
             approved by Amgen medical monitor

          -  Participants with elevated cardiac troponin above the manufacturer's 99th percentile
             upper reference limit for ADVIA Centaur XP assay at screening performed by the central
             laboratory

          -  Participants with evidence of recent cardiac injury at screening based on creatine
             kinase-muscle/brain (CK-MB), N-terminal prohormone of brain natriuretic peptide
             (NT-pro-BNP), and electrocardiogram (ECG)

          -  Other exclusion criteria may apply

          -  (Acute myeloid leukemia Part 3d only) History of QT prolongation, torsades de pointes,
             ventricular tachycardia and cardiac arrest
      
Maximum Eligible Age:85 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Multiple Myeloma (MM) Part 1a Incidence of dose-limiting toxicities (DLTs)
Time Frame:Up to 6 months
Safety Issue:
Description:Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the maximum tolerated dose (MTD) for two-consecutive days per week dosing schedule (QD2)

Secondary Outcome Measures

Measure:MM Part 1a BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts
Time Frame:6 months on treatment
Safety Issue:
Description:Demonstrate inactivation of myeloid cell leukemia sequence 1 (MCL1) by the increase of active Bcl 2 associated X protein (BAX) and caspase 3 in circulating monocytes and/or the decrease of circulating monocytes in AMG 176 QD2 treated subjects
Measure:MM Part 1a Overall response (OR) according to International Myeloma Working Group uniform response criteria (IMWG-URC) for MM subjects
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
Measure:MM Part 1a Progression-free survival (PFS)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
Measure:MM Part 1a Time to response
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
Measure:MM Part 1a Duration of response (DOR)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
Measure:MM Part 1b BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts
Time Frame:6 months on treatment
Safety Issue:
Description:Demonstrate inactivation of MCL1 by the increase of active BAX and caspase 3 in circulating monocytes and /or the decrease of circulating monocytes in AMG 176 QW treated subjects
Measure:MM Part 1b Overall response (OR) according to IMWG-URC for MM subjects
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
Measure:MM Part 1b Progression free survival (PFS)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
Measure:MM Part 1b Time to response
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
Measure:MM Part 1b Duration of response (DOR)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
Measure:AML Part 3a, 3b and 3c Overall response (OR) according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
Measure:AML Part 3a, 3b and 3c Event free survival (EFS)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
Measure:AML Part 3a, 3b and 3c Time to response
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
Measure:AML Part 3a, 3b and 3c Duration of response (DOR)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
Measure:AML Part 3d Incidence of treatment-emergent adverse events
Time Frame:3 weeks on treatment
Safety Issue:
Description:Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
Measure:AML Part 3d Incidence of clinically significant changes in vital signs
Time Frame:3 weeks on treatment
Safety Issue:
Description:Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
Measure:AML Part 3d Incidence of clinically significant changes in ECGs
Time Frame:3 weeks on treatment
Safety Issue:
Description:Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
Measure:AML Part 3d Incidence of clinically significant changes in clinical laboratory tests
Time Frame:3 weeks on treatment
Safety Issue:
Description:Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
Measure:AML Part 4 Overall response (OR) according to the 2017 ELN criteria in AML subjects
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
Measure:AML Part 4 Event free survival (EFS)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
Measure:AML Part 4 Time to response
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
Measure:AML Part 4 Duration of response (DOR)
Time Frame:6 months on treatment
Safety Issue:
Description:Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

Details

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

Last Updated

June 3, 2021