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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma; Relapsed or Refractory Acute Myeloid Leukemia
• Intervention / Treatment: Drug: AMG 176; Drug: Itraconazole; Drug: Azacitidine

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 participants with relapsed or refractory multiple myeloma and participants with relapsed or refractory acute myeloid leukemia The study will be conducted in five parts.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Tom Baker Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Cancer Centre
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum der Rheinisch-Westfaelischen Technischen Hochschule Aachen
  • Bonn, Germany, 53127
    • Universitaetsklinikum Bonn
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
  • Wuerzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
  • Okayama
    • Okayama-shi, Okayama, Japan, 701-1192
      • National Hospital Organization Okayama Medical Center
  • Tokyo
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • Ntt Medical Center Tokyo
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 [MM] participants) Pathologically documented, multiple myeloma relapsed or refractory disease after at least 2 lines of therapy
• (MM participants only) Measurable disease per the International Myeloma Working Group response criteria
• (Acute myeloid leukemia [AML] participants) AML as defined by the World Health Organization 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 participants only) More than 5% blasts in bone marrow and Circulating white blood cells < 25,000/ul.
• Must be willing and able to undergo a core bone marrow biopsy (MM participants only) and bone marrow aspirate (MM and AML participants) at screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2,
• (MM partiicpants 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 participants 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 participants only) MM with Immunoglobulin M subtype
• (MM participants only) Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes syndrome
• (MM participants only) Existing plasma cell leukemia
• (MM participants only) Waldenstrom's macroglobulinemia
• (MM participants only) Amyloidosis
• 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, N-terminal prohormone of brain natriuretic peptide, and electrocardiogram
• Other exclusion criteria may apply
• (AML Part 3d only) History of QT prolongation, torsades de pointes, ventricular tachycardia and cardiac arrest
• History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with medical monitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG 176 - Part 1a; Part 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.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP)
Experimental: AMG 176 - Part 1b; Part 1b - Participants with multiple myeloma (MM) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP)
Experimental: AMG 176 - Part 3a; Part 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.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP)
Experimental: AMG 176 - Part 3b; Part 3b - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP)
Experimental: AMG 176 - Part 3c; Part 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.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP)
Experimental: AMG 176 - Part 3d; Part 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.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP); Drug: Itraconazole; Non-investigational product
Experimental: AMG 176 - Part 4; Part 4 - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, either once a week (QW) followed by 6 days break, or once a day, for two-consecutive days (QD2), in combination with azacitidine.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP); Drug: Azacitidine; Non-investigational product
Experimental: AMG 176 - Part 5; Part 5 - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion at the maximum tolerated combination dose from Part 4, either once a week (QW) followed by 6 days break, or once a day, for two-consecutive days (QD2), in combination with azacitidine.	Drug: AMG 176; Study Drug; Other Names: Study Investigational Product (IP); Drug: Azacitidine; Non-investigational product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Myeloma (MM) Part 1a Incidence of dose-limiting toxicities (DLTs)	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)	Up to 6 months
MM Part 1a Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 18 months
MM Part 1a Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 18 months
MM Part 1a Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 6 months
MM Part 1a Incidence of clinically significant changes in electrocardiograms (ECGs)	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 6 months
MM Part 1a Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 6 months
MM Part 1a Pharmacokinetic parameters for AMG 176: area under the concentration-time curve (AUC)	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
MM Part 1a Pharmacokinetic parameters for AMG 176: clearance (CL)	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
MM Part 1a Pharmacokinetic parameters for AMG 176: half-life (t1/2)	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
MM Part 1b Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a once weekly (QW) dosing schedule	Up to 6 months
MM Part 1b Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 18 months
MM Part 1b Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 18 months
MM Part 1b Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 6 months
MM Part 1b Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 6 months
MM Part 1b Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 6 months
MM Part 1b Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
MM Part 1b Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
MM Part 1b Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
MM Part 1b Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Acute Myeloid Leukemia (AML) Part 3a Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3a Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 18 months
AML Part 3a Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 18 months
AML Part 3a Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3a Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3a Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3a Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
AML Part 3a Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
AML Part 3a Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
AML Part 3a Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
AML Part 3b Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3b Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 18 months
AML Part 3b Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 18 months
AML Part 3b Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3b Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3b Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
AML Part 3b Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
AML Part 3b Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
AML Part 3b Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
AML Part 3b Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
AML Part 3c Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
AML Part 3c Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 18 months
AML Part 3c Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 18 months
AML Part 3c Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
AML Part 3c Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
AML Part 3c Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
AML Part 3c Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
AML Part 3c Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
AML Part 3c Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
AML Part 3c Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: Cmax	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: AUC	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: CL	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: t1/2	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 4 Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the maximum tolerated combination dose (MTCD) of AMG 176 in combination with azacitidine	Up to 6 months
AML Part 4 Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 18 months
AML Part 4 Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 18 months
AML Part 4 Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 6 months
AML Part 4 Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 6 months
AML Part 4 Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 6 months
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: CL	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
AML Part 5 Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 18 months
AML Part 5 Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 18 months
AML Part 5 Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 6 months
AML Part 5 Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 6 months
AML Part 5 Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 6 months
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: CL	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
MM Part 1a Pharmacokinetic (PK) parameters for AMG 176: maximum observed concentration (Cmax)	Evaluate the pharmacokinetics (PK) of AMG 176 when administered as monotherapy QD2	1 month on treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MM Part 1a BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts	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	6 months on treatment
MM Part 1a Overall response (OR) according to International Myeloma Working Group uniform response criteria (IMWG-URC) for MM subjects	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
MM Part 1a Progression-free survival (PFS)	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
MM Part 1a Time to response	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
MM Part 1a Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
MM Part 1b Overall response (OR) according to IMWG-URC for MM subjects	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
MM Part 1b Progression free survival (PFS)	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
MM Part 1b Time to response	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
MM Part 1b Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
AML Part 3a, 3b and 3c Overall response (OR) according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017)	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
AML Part 3a, 3b and 3c Event free survival (EFS)	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
AML Part 3a, 3b and 3c Time to response	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
AML Part 3a, 3b and 3c Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
AML Part 3d Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 3d Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 3d Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 3d Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
AML Part 4 Overall response (OR) according to the 2017 ELN criteria in AML subjects	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
AML Part 4 Event free survival (EFS)	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
AML Part 4 Time to response	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
AML Part 4 Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
AML Part 5 OR according to the 2017 ELN criteria in AML subjects	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
AML Part 5 EFS	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
AML Part 5 Time to response	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
AML Part 5 DOR	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
MM Part 1b BAX and caspase 3 expression in circulating monocytes and/or circulating monocyte counts	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	6 months on treatment

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2016
• Primary Completion (Estimated): June 28, 2024
• Study Completion (Estimated): June 28, 2024

Study Registration Dates

• First Submitted: December 22, 2015
• First Submitted That Met QC Criteria: February 3, 2016
• First Posted (Estimated): February 5, 2016

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Azacitidine; Itraconazole
• Other Study ID Numbers: 20150161; 2015-004777-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No