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

Sponsor

Amgen (Industry)

Overall Status

Suspended

CT.gov ID

NCT02675452

Collaborator

(none)

175

Enrollment

Locations

Arms

96.5

Anticipated Duration (Months)

7.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Multiple Myeloma Relapsed or Refractory Acute Myeloid Leukemia	Drug: AMG 176 Drug: Azacitidine Drug: Itraconazole	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

175 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 13, 2016

Anticipated Primary Completion Date :

Oct 28, 2023

Anticipated Study Completion Date :

Jun 27, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	University of California Davis Medical Center	Sacramento	California	United States	95817
3	University of Colorado	Aurora	Colorado	United States	80045
4	Northside Hospital	Atlanta	Georgia	United States	30342
5	University of Chicago Hospital	Chicago	Illinois	United States	60637
6	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
7	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
8	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
9	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
10	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
11	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
12	The Alfred Hospital	Melbourne	Victoria	Australia	3004
13	The Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
14	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 2T9
15	University Health Network-Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
16	Universitätsklinikum der Rheinisch-Westfälischen Technischen Hochschule Aachen	Aachen		Germany	52074
17	Universitätsklinikum Bonn	Bonn		Germany	53127
18	Universitatsklinikum Ulm	Ulm		Germany	89081
19	Universitätsklinikum Würzburg	Würzburg		Germany	97080
20	National Hospital Organization Nagoya Medical Center	Nagoya-shi	Aichi	Japan	460-0001
21	National Cancer Center Hospital East	Kashiwa-shi	Chiba	Japan	277-8577
22	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka	Japan	811-1395
23	National Hospital Organization Okayama Medical Center	Okayama-shi	Okayama	Japan	701-1192
24	NTT Medical Center Tokyo	Shinagawa-ku	Tokyo	Japan	141-8625