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

Summary:

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

Trial Description

Primary Outcome:

  • Multiple Myeloma 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, including, but not limited to, maximum observed concentration (Cmax)
  • MM Part 1a Pharmacokinetic parameters for AMG 176, including, but not limited to, area under the concentration-time curve (AUC)
  • MM Part 1a Pharmacokinetic parameters for AMG 176, including, but not limited to, clearance (CL)
  • MM Part 1a Pharmacokinetic parameters for AMG 176, including, but not limited to, 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 physical examinations
  • 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 including, but not limited to Cmax
  • MM Part 1b Pharmacokinetic parameters for AMG 176 including, but not limited to AUC
  • MM Part 1b Pharmacokinetic parameters for AMG 176 including, but not limited to CL
  • MM Part 1b Pharmacokinetic parameters for AMG 176 including, but not limited to t1/2
  • MM Part 2 Incidence of DLTs
  • MM Part 2 Incidence of treatment-related adverse events
  • MM Part 2 Incidence of treatment-emergent adverse events
  • MM Part 2 Incidence of clinically significant changes in vital signs
  • MM Part 2 Incidence of clinically significant changes in physical examinations
  • MM Part 2 Incidence of clinically significant changes in ECGs
  • MM Part 2 Incidence of clinically significant changes in clinical laboratory tests
  • MM Part 2 Pharmacokinetic parameters for AMG 176 and carfilzomib including, but not limited to Cmax
  • MM Part 2 Pharmacokinetic parameters for AMG 176 and carfilzomib including, but not limited to AUC
  • MM Part 2 Pharmacokinetic parameters for AMG 176 and carfilzomib including, but not limited to CL
  • MM Part 2 Pharmacokinetic parameters for AMG 176 and carfilzomib including, but not limited to t1/2
  • Acute Myeloid Leukemia (AML) Part 3 Incidence of DLTs
  • AML Part 3 Incidence of treatment-related adverse events
  • AML Part 3 Incidence of treatment-emergent adverse events
  • AML Part 3 Incidence of clinically significant changes in vital signs
  • AML Part 3 Incidence of clinically significant changes in physical examinations
  • AML Part 3 Incidence of clinically significant changes in ECGs
  • AML Part 3 Incidence of clinically significant changes in clinical laboratory tests
  • AML Part 3 Pharmacokinetic parameters for AMG 176 including, but not limited to Cmax
  • AML Part 3 Pharmacokinetic parameters for AMG 176 including, but not limited to AUC
  • AML Part 3 Pharmacokinetic parameters for AMG 176 including, but not limited to CL
  • AML Part 3 Pharmacokinetic parameters for AMG 176 including, but not limited to 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 physical examinations
  • 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 including, but not limited to, Cmax
  • AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine including, but not limited to, AUC
  • AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine including, but not limited to, CL
  • AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine including, but not limited to, 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 OR according to IMWG-URC for MM progression-free survival (PFS)
  • MM Part 1a OR according to IMWG-URC for MM time to response
  • MM Part 1a OR according to IMWG-URC for MM duration of response (DOR)
  • MM Part 1b BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts
  • MM Part 1b OR according to IMWG-URC for MM subjects
  • MM Part 1b OR according to IMWG-URC for MM PFS
  • MM Part 1b OR according to IMWG-URC for MM time to response
  • MM Part 1b OR according to IMWG-URC for MM DOR
  • MM Part 2 BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts
  • MM Part 2 OR according to IMWG-URC for MM subjects
  • MM Part 2 OR according to IMWG-URC for MM PFS
  • MM Part 2 OR according to IMWG-URC for MM time to response
  • MM Part 2 OR according to IMWG-URC for MM DOR
  • AML Part 3 OR according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017) in AML subjects
  • AML Part 3 OR according to the 2017 ELN criteria (Döhner et al, 2017) in AML event free survival (EFS)
  • AML Part 3 OR according to the 2017 ELN criteria (Döhner et al, 2017) in AML time to response
  • AML Part 3 OR according to the 2017 ELN criteria (Döhner et al, 2017) in AML DOR
  • AML Part 4 OR according to the 2017 ELN criteria in AML subjects
  • AML Part 4 OR according to the 2017 ELN criteria in AML EFS
  • AML Part 4 OR according to the 2017 ELN criteria in AML time to response
  • AML Part 4 OR according to the 2017 ELN criteria in AML DOR
This is a Phase 1, first-in-human, multicentre; 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.

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society