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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02675452
Recruitment Status : Recruiting
First Posted : February 5, 2016
Last Update Posted : January 5, 2023
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Description
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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
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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 13, 2016
Estimated Primary Completion Date : February 29, 2024
Estimated Study Completion Date : January 8, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Study Investigational Product (IP)

Drug: Azacitidine
Non-investigational product


Outcome Measures
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Primary Outcome Measures :
  1. Multiple Myeloma (MM) Part 1a Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 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)

  2. MM Part 1a Incidence of treatment-related adverse events [ Time Frame: 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

  3. MM Part 1a Incidence of treatment-emergent adverse events [ Time Frame: 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

  4. MM Part 1a Incidence of clinically significant changes in vital signs [ Time Frame: 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

  5. MM Part 1a Incidence of clinically significant changes in electrocardiograms (ECGs) [ Time Frame: 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

  6. MM Part 1a Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: 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

  7. MM Part 1a Pharmacokinetic parameters for AMG 176: maximum observed concentration (Cmax) [ Time Frame: 1 month on treatment ]
    Evaluate the pharmacokinetics (PK) of AMG 176 when administered as monotherapy QD2

  8. MM Part 1a Pharmacokinetic parameters for AMG 176: area under the concentration-time curve (AUC) [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QD2

  9. MM Part 1a Pharmacokinetic parameters for AMG 176: clearance (CL) [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QD2

  10. MM Part 1a Pharmacokinetic parameters for AMG 176: half-life (t1/2) [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QD2

  11. MM Part 1b Incidence of DLTs [ Time Frame: 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

  12. MM Part 1b Incidence of treatment-related adverse events [ Time Frame: 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

  13. MM Part 1b Incidence of treatment-emergent adverse events [ Time Frame: 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

  14. MM Part 1b Incidence of clinically significant changes in vital signs [ Time Frame: 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

  15. MM Part 1b Incidence of clinically significant changes in ECGs [ Time Frame: 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

  16. MM Part 1b Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: 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

  17. MM Part 1b Pharmacokinetic parameters for AMG 176: Cmax [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  18. MM Part 1b Pharmacokinetic parameters for AMG 176: AUC [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  19. MM Part 1b Pharmacokinetic parameters for AMG 176: CL [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  20. MM Part 1b Pharmacokinetic parameters for AMG 176: t1/2 [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  21. Acute Myeloid Leukemia (AML) Part 3a Incidence of DLTs [ Time Frame: 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

  22. AML Part 3a Incidence of treatment-related adverse events [ Time Frame: 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

  23. AML Part 3a Incidence of treatment-emergent adverse events [ Time Frame: 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

  24. AML Part 3a Incidence of clinically significant changes in vital signs [ Time Frame: 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

  25. AML Part 3a Incidence of clinically significant changes in ECGs [ Time Frame: 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

  26. AML Part 3a Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: 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

  27. AML Part 3a Pharmacokinetic parameters for AMG 176: Cmax [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QD2

  28. AML Part 3a Pharmacokinetic parameters for AMG 176: AUC [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QD2

  29. AML Part 3a Pharmacokinetic parameters for AMG 176: CL [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QD2

  30. AML Part 3a Pharmacokinetic parameters for AMG 176: t1/2 [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QD2

  31. AML Part 3b Incidence of DLTs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML

  32. AML Part 3b Incidence of treatment-related adverse events [ Time Frame: Up to 18 months ]
    Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML

  33. AML Part 3b Incidence of treatment-emergent adverse events [ Time Frame: Up to 18 months ]
    Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML

  34. AML Part 3b Incidence of clinically significant changes in vital signs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML

  35. AML Part 3b Incidence of clinically significant changes in ECGs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML

  36. AML Part 3b Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML

  37. AML Part 3b Pharmacokinetic parameters for AMG 176: Cmax [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  38. AML Part 3b Pharmacokinetic parameters for AMG 176: AUC [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  39. AML Part 3b Pharmacokinetic parameters for AMG 176: CL [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  40. AML Part 3b Pharmacokinetic parameters for AMG 176: t1/2 [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy QW

  41. AML Part 3c Incidence of DLTs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML

  42. AML Part 3c Incidence of treatment-related adverse events [ Time Frame: Up to 18 months ]
    Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML

  43. AML Part 3c Incidence of treatment-emergent adverse events [ Time Frame: Up to 18 months ]
    Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML

  44. AML Part 3c Incidence of clinically significant changes in vital signs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML

  45. AML Part 3c Incidence of clinically significant changes in ECGs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML

  46. AML Part 3c Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML

  47. AML Part 3c Pharmacokinetic parameters for AMG 176: Cmax [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan

  48. AML Part 3c Pharmacokinetic parameters for AMG 176: AUC [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan

  49. AML Part 3c Pharmacokinetic parameters for AMG 176: CL [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan

  50. AML Part 3c Pharmacokinetic parameters for AMG 176: t1/2 [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan

  51. AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: Cmax [ Time Frame: 3 weeks on treatment ]
    Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  52. AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: AUC [ Time Frame: 3 weeks on treatment ]
    Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  53. AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: CL [ Time Frame: 3 weeks on treatment ]
    Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  54. AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: t1/2 [ Time Frame: 3 weeks on treatment ]
    Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  55. AML Part 4 Incidence of DLTs [ Time Frame: 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

  56. AML Part 4 Incidence of treatment-related adverse events [ Time Frame: 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

  57. AML Part 4 Incidence of treatment-emergent adverse events [ Time Frame: 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

  58. AML Part 4 Incidence of clinically significant changes in vital signs [ Time Frame: 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

  59. AML Part 4 Incidence of clinically significant changes in ECGs [ Time Frame: 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

  60. AML Part 4 Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: 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

  61. AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination

  62. AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination

  63. AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: CL [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination

  64. AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2 [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination

  65. AML Part 5 Incidence of treatment-related adverse events [ Time Frame: Up to 18 months ]
    Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML

  66. AML Part 5 Incidence of treatment-emergent adverse events [ Time Frame: Up to 18 months ]
    Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML

  67. AML Part 5 Incidence of clinically significant changes in vital signs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML

  68. AML Part 5 Incidence of clinically significant changes in ECGs [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML

  69. AML Part 5 Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: Up to 6 months ]
    Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML

  70. AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination

  71. AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination

  72. AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: CL [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination

  73. AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2 [ Time Frame: 1 month on treatment ]
    Evaluate the PK of AMG 176 and azacitidine when administered in combination


Secondary Outcome Measures :
  1. MM Part 1a BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts [ Time Frame: 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

  2. 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 ]
    Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM

  3. MM Part 1a Progression-free survival (PFS) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM

  4. MM Part 1a Time to response [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM

  5. MM Part 1a Duration of response (DOR) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM

  6. MM Part 1b BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts [ Time Frame: 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

  7. MM Part 1b Overall response (OR) according to IMWG-URC for MM subjects [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM

  8. MM Part 1b Progression free survival (PFS) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM

  9. MM Part 1b Time to response [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM

  10. MM Part 1b Duration of response (DOR) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM

  11. 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 ]
    Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML

  12. AML Part 3a, 3b and 3c Event free survival (EFS) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML

  13. AML Part 3a, 3b and 3c Time to response [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML

  14. AML Part 3a, 3b and 3c Duration of response (DOR) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML

  15. AML Part 3d Incidence of treatment-emergent adverse events [ Time Frame: 3 weeks on treatment ]
    Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  16. AML Part 3d Incidence of clinically significant changes in vital signs [ Time Frame: 3 weeks on treatment ]
    Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  17. AML Part 3d Incidence of clinically significant changes in ECGs [ Time Frame: 3 weeks on treatment ]
    Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  18. AML Part 3d Incidence of clinically significant changes in clinical laboratory tests [ Time Frame: 3 weeks on treatment ]
    Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML

  19. AML Part 4 Overall response (OR) according to the 2017 ELN criteria in AML subjects [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

  20. AML Part 4 Event free survival (EFS) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

  21. AML Part 4 Time to response [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

  22. AML Part 4 Duration of response (DOR) [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

  23. AML Part 5 OR according to the 2017 ELN criteria in AML subjects [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

  24. AML Part 5 EFS [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

  25. AML Part 5 Time to response [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML

  26. AML Part 5 DOR [ Time Frame: 6 months on treatment ]
    Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 [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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02675452


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
More Information
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Additional Information:

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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02675452    
Other Study ID Numbers: 20150161
2015-004777-32 ( EudraCT Number )
First Posted: February 5, 2016    Key Record Dates
Last Update Posted: January 5, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
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.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
 Immunoproliferative Disorders
Immune System Diseases
Itraconazole
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists