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

Titre officiel

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

Sommaire:

Au moins une dose d’AMG 176 produira une innocuité et une tolérabilité acceptables chez les sujets atteints d’un myélome récidivant ou réfractaire et les sujets atteints d’une leucémie aiguë myéloïde récidivante ou réfractaire

Description de l'essai

Primary Outcome:

• Multiple Myeloma (MM) Part 1a Incidence of dose-limiting toxicities (DLTs)
• MM Part 1a Incidence of treatment-related adverse events
• MM Part 1a Incidence of treatment-emergent adverse events
• MM Part 1a Incidence of clinically significant changes in vital signs
• MM Part 1a Incidence of clinically significant changes in electrocardiograms (ECGs)
• MM Part 1a Incidence of clinically significant changes in clinical laboratory tests
• MM Part 1a Pharmacokinetic parameters for AMG 176: maximum observed concentration (Cmax)
• MM Part 1a Pharmacokinetic parameters for AMG 176: area under the concentration-time curve (AUC)
• MM Part 1a Pharmacokinetic parameters for AMG 176: clearance (CL)
• MM Part 1a Pharmacokinetic parameters for AMG 176: half-life (t1/2)
• MM Part 1b Incidence of DLTs
• MM Part 1b Incidence of treatment-related adverse events
• MM Part 1b Incidence of treatment-emergent adverse events
• MM Part 1b Incidence of clinically significant changes in vital signs
• MM Part 1b Incidence of clinically significant changes in ECGs
• MM Part 1b Incidence of clinically significant changes in clinical laboratory tests
• MM Part 1b Pharmacokinetic parameters for AMG 176: Cmax
• MM Part 1b Pharmacokinetic parameters for AMG 176: AUC
• MM Part 1b Pharmacokinetic parameters for AMG 176: CL
• MM Part 1b Pharmacokinetic parameters for AMG 176: t1/2
• Acute Myeloid Leukemia (AML) Part 3a Incidence of DLTs
• AML Part 3a Incidence of treatment-related adverse events
• AML Part 3a Incidence of treatment-emergent adverse events
• AML Part 3a Incidence of clinically significant changes in vital signs
• AML Part 3a Incidence of clinically significant changes in ECGs
• AML Part 3a Incidence of clinically significant changes in clinical laboratory tests
• AML Part 3a Pharmacokinetic parameters for AMG 176: Cmax
• AML Part 3a Pharmacokinetic parameters for AMG 176: AUC
• AML Part 3a Pharmacokinetic parameters for AMG 176: CL
• AML Part 3a Pharmacokinetic parameters for AMG 176: t1/2
• AML Part 3b Incidence of DLTs
• AML Part 3b Incidence of treatment-related adverse events
• AML Part 3b Incidence of treatment-emergent adverse events
• AML Part 3b Incidence of clinically significant changes in vital signs
• AML Part 3b Incidence of clinically significant changes in ECGs
• AML Part 3b Incidence of clinically significant changes in clinical laboratory tests
• AML Part 3b Pharmacokinetic parameters for AMG 176: Cmax
• AML Part 3b Pharmacokinetic parameters for AMG 176: AUC
• AML Part 3b Pharmacokinetic parameters for AMG 176: CL
• AML Part 3b Pharmacokinetic parameters for AMG 176: t1/2
• AML Part 3c Incidence of DLTs
• AML Part 3c Incidence of treatment-related adverse events
• AML Part 3c Incidence of treatment-emergent adverse events
• AML Part 3c Incidence of clinically significant changes in vital signs
• AML Part 3c Incidence of clinically significant changes in ECGs
• AML Part 3c Incidence of clinically significant changes in clinical laboratory tests
• AML Part 3c Pharmacokinetic parameters for AMG 176: Cmax
• AML Part 3c Pharmacokinetic parameters for AMG 176: AUC
• AML Part 3c Pharmacokinetic parameters for AMG 176: CL
• AML Part 3c Pharmacokinetic parameters for AMG 176: t1/2
• AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: Cmax
• AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: AUC
• AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: CL
• AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: t1/2
• AML Part 4 Incidence of DLTs
• AML Part 4 Incidence of treatment-related adverse events
• AML Part 4 Incidence of treatment-emergent adverse events
• AML Part 4 Incidence of clinically significant changes in vital signs
• AML Part 4 Incidence of clinically significant changes in ECGs
• AML Part 4 Incidence of clinically significant changes in clinical laboratory tests
• AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax
• AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC
• AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: CL
• AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2
• AML Part 5 Incidence of treatment-related adverse events
• AML Part 5 Incidence of treatment-emergent adverse events
• AML Part 5 Incidence of clinically significant changes in vital signs
• AML Part 5 Incidence of clinically significant changes in ECGs
• AML Part 5 Incidence of clinically significant changes in clinical laboratory tests
• AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax
• AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC
• AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: CL
• AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2

Secondary Outcome:

• MM Part 1a BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts
• MM Part 1a Overall response (OR) according to International Myeloma Working Group uniform response criteria (IMWG-URC) for MM subjects
• MM Part 1a Progression-free survival (PFS)
• MM Part 1a Time to response
• MM Part 1a Duration of response (DOR)
• MM Part 1b BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts
• MM Part 1b Overall response (OR) according to IMWG-URC for MM subjects
• MM Part 1b Progression free survival (PFS)
• MM Part 1b Time to response
• MM Part 1b Duration of response (DOR)
• AML Part 3a, 3b and 3c Overall response (OR) according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017)
• AML Part 3a, 3b and 3c Event free survival (EFS)
• AML Part 3a, 3b and 3c Time to response
• AML Part 3a, 3b and 3c Duration of response (DOR)
• AML Part 3d Incidence of treatment-emergent adverse events
• AML Part 3d Incidence of clinically significant changes in vital signs
• AML Part 3d Incidence of clinically significant changes in ECGs
• AML Part 3d Incidence of clinically significant changes in clinical laboratory tests
• AML Part 4 Overall response (OR) according to the 2017 ELN criteria in AML subjects
• AML Part 4 Event free survival (EFS)
• AML Part 4 Time to response
• AML Part 4 Duration of response (DOR)
• AML Part 5 OR according to the 2017 ELN criteria in AML subjects
• AML Part 5 EFS
• AML Part 5 Time to response
• AML Part 5 DOR

This is a Phase 1, first-in-human, multicentre; 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.

Voir cet essai sur ClinicalTrials.gov