Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies

Sponsor
Amgen (Industry)
Overall Status
Terminated
CT.gov ID
NCT03465540
Collaborator
(none)
24
Enrollment
21
Locations
8
Arms
12.4
Actual Duration (Months)
1.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs) and/or biologically active doses.

Detailed Description

This is a first-in-human (FIH), multicenter, non-randomized, open-label, phase 1 study evaluating AMG 397 administered orally once weekly, as part of a 28-day treatment cycle in adult subjects with selected relapsed or refractory hematological malignancies

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies
Actual Study Start Date :
Aug 17, 2018
Actual Primary Completion Date :
Aug 29, 2019
Actual Study Completion Date :
Aug 29, 2019

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part 1A: AMG 397 Dose Escalation

This arm includes subjects with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL).

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Experimental: Part 1B: AMG 397 Dose Escalation

This arm includes subjects with acute myeloid leukemia (AML).

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Experimental: Part 2A: AMG 397 Monotherapy

This arm includes subjects with AML or myelodysplastic syndrome (MDS).

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Experimental: Part 2B: AMG 397 Monotherapy

This arm includes subjects with AML in Japan only.

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Experimental: Part 2C: AMG 397 Monotherapy

This arm includes subjects with MM.

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Experimental: Part 3A: AMG 397 + Azacitidine Combotherapy

This arm includes subjects MDS.

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Drug: Azacitidine
Azacitidine will be administered intravenously (IV) or subcutaneously (SC) daily for the first 7 days of a 28-day cycle.

Experimental: Part 3B: AMG 397+ Azacitidine Combotherapy

This arm includes subjects AML.

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Drug: Azacitidine
Azacitidine will be administered intravenously (IV) or subcutaneously (SC) daily for the first 7 days of a 28-day cycle.

Experimental: Part 3C: AMG 397+ Dexamethasone Combotherapy

This arm includes subjects MM.

Drug: AMG 397
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Drug: Dexamethasone
Dexamethasone will be administered intravenously (IV) or orally on Days 1, 8, 15, and 22 of each 28-day cycle.

Outcome Measures

Primary Outcome Measures

  1. Part 1A: Subject Incidence of Dose-Limiting Toxicity [28 days]

  2. Part 1A: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  3. Part 1A: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  4. Part 1A: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  5. Part 1A: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  6. Part 1A: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  7. Part 1A: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

  8. Part 1B: Subject Incidence of Dose-Limiting Toxicity [28 days]

  9. Part 1B: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  10. Part 1B: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  11. Part 1B: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  12. Part 1B: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  13. Part 1B: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  14. Part 1B: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

  15. Part 2A: Subject Incidence of Dose-Limiting Toxicity [28 days]

  16. Part 2A: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  17. Part 2A: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  18. Part 2A: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  19. Part 2A: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  20. Part 2A: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  21. Part 2A: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

  22. Part 2B: Subject Incidence of Dose-Limiting Toxicity [28 days]

  23. Part 2B: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  24. Part 2B: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  25. Part 2B: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  26. Part 2B: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  27. Part 2B: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  28. Part 2B: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

  29. Part 2B: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  30. Part 2B: Area Under the Concentration-time Curve (AUC) for AMG 397 [Up to 6 months]

  31. Part 2B: Clearance (CL) of AMG 397 [Up to 6 months]

  32. Part 2B: Half-life (t1/2) of AMG 397 [Up to 6 months]

  33. Part 2C: Subject Incidence of Dose-Limiting Toxicity [28 days]

  34. Part 2C: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  35. Part 2C: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  36. Part 2C: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  37. Part 2C: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  38. Part 2C: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  39. Part 2C: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

  40. Part 3A: Subject Incidence of Dose-Limiting Toxicity [28 days]

  41. Part 3A: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  42. Part 3A: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  43. Part 3A: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  44. Part 3A: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  45. Part 3A: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  46. Part 3A: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

  47. Part 3B: Subject Incidence of Dose-Limiting Toxicity [28 days]

  48. Part 3B: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  49. Part 3B: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  50. Part 3B: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  51. Part 3B: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  52. Part 3B: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  53. Part 3B: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

  54. Part 3C: Subject Incidence of Dose-Limiting Toxicity [28 days]

  55. Part 3C: Incidence of Treatment-Emergent Adverse Events [Up to 19 months]

  56. Part 3C: Incidence of Treatment-Related Adverse Events [Up to 19 months]

  57. Part 3C: Incidence of Clinically Significant Changes in Vital Signs [Up to 8 months]

  58. Part 3C: Incidence of Clinically Significant Changes in Physical Examinations [Up to 8 months]

  59. Part 3C: Incidence of Clinically Significant Changes in Electrocardiograms (ECGs) [Up to 8 months]

  60. Part 3C: Incidence of Clinically Significant Changes in Clinical Laboratory Tests [Up to 8 months]

Secondary Outcome Measures

  1. Part 1A: Objective Response Rate (ORR) for Multiple Myeloma (MM) Subjects [Up to 19 months]

    Response criteria per International Myeloma Working Group - Uniform Response Criteria (IMWG-URC).

  2. Part 1A: Objective Response Rate (ORR) for Non-Hodgkin's Lymphoma (HNL) Subjects [Up to 19 months]

    Response criteria per Lugano Classification.

  3. Part 1A: Progression-free survival (PFS) [Up to 19 months]

  4. Part 1A: Overall Survival (OS) [Up to 19 months]

  5. Part 1A: Time to Response [Up to 19 months]

  6. Part 1A: Duration of Response (DoR) [Up to 19 months]

  7. Part 1A: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  8. Part 1A: Time of Maximum Observed Concentration (Tmax) of AMG 397 [Up to 6 months]

  9. Part 1A: Area Under the Concentration Time Curve (AUC) of AMG 397 [Up to 6 months]

  10. Part 1A: Clearance (CL) of AMG 397 [Up to 6 months]

  11. Part 1A: Half-life (t1/2) of AMG 397 [Up to 6 months]

  12. Part 1B: Objective Response Rate (ORR) for Acute Myeloid Leukemia (AML) Subjects [Up to 19 months]

    Response criteria per Revised International Working Group (IWG).

  13. Part 1B: Objective Response Rate (ORR) for Myelodysplastic Syndrome (MDS) Subjects [Up to 19 months]

    Response criteria per Revised International Working Group (IWG).

  14. Part 1B: Progression-free survival (PFS) [Up to 19 months]

  15. Part 1B: Overall Survival (OS) [Up to 19 months]

  16. Part 1B: Time to Response [Up to 19 months]

  17. Part 1B: Duration of Response (DoR) [Up to 19 months]

  18. Part 1B: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  19. Part 1B: Time of Maximum Observed Concentration (Tmax) of AMG 397 [Up to 6 months]

  20. Part 1B: Area Under the Concentration Time Curve (AUC) of AMG 397 [Up to 6 months]

  21. Part 1B: Clearance (CL) of AMG 397 [Up to 6 months]

  22. Part 1B: Half-life (t1/2) of AMG 397 [Up to 6 months]

  23. Part 2A: Objective Response Rate (ORR) for Myelodysplastic Syndrome (MDS) Subjects [Up to 19 months]

    Response criteria per Revised International Working Group (IWG).

  24. Part 2A: Objective Response Rate (ORR) for Acute Myeloid Leukemia (AML) Subjects [Up to 19 months]

    Response criteria per Revised International Working Group (IWG).

  25. Part 2A: Progression-free survival (PFS) [Up to 19 months]

  26. Part 2A: Overall Survival (OS) [Up to 19 months]

  27. Part 2A: Time to Response [Up to 19 months]

  28. Part 2A: Duration of Response (DoR) [Up to 19 months]

  29. Part 2A: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  30. Part 2A: Time of Maximum Observed Concentration (Tmax) of AMG 397 [Up to 6 months]

  31. Part 2A: Area Under the Concentration Time Curve (AUC) of AMG 397 [Up to 6 months]

  32. Part 2A: Clearance (CL) of AMG 397 [Up to 6 months]

  33. Part 2A: Half-life (t1/2) of AMG 397 [Up to 6 months]

  34. Part 2B: Objective Response Rate (ORR) for Acute Myeloid Leukemia (AML) Subjects [Up to 19 months]

    Response criteria per Revised International Working Group (IWG).

  35. Part 2B: Progression-free survival (PFS) [Up to 19 months]

  36. Part 2B: Overall Survival (OS) [Up to 19 months]

  37. Part 2B: Time to Response [Up to 19 months]

  38. Part 2B: Duration of Response (DoR) [Up to 19 months]

  39. Part 2B: Time of Maximum Observed Concentration (Tmax) of AMG 397 [Up to 6 months]

  40. Part 2C: Objective Response Rate (ORR) for Multiple Myeloma (MM) Subjects [Up to 19 months]

    Response criteria per International Myeloma Working Group - Uniform Response Criteria (IMWG-URC).

  41. Part 2C: Progression-free survival (PFS) [Up to 19 months]

  42. Part 2C: Overall Survival (OS) [Up to 19 months]

  43. Part 2C: Time to Response [Up to 19 months]

  44. Part 2C: Duration of Response (DoR) [Up to 19 months]

  45. Part 2C: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  46. Part 2C: Time of Maximum Observed Concentration (Tmax) of AMG 397 [Up to 6 months]

  47. Part 2C: Area Under the Concentration Time Curve (AUC) of AMG 397 [Up to 6 months]

  48. Part 2C: Clearance (CL) of AMG 397 [Up to 6 months]

  49. Part 2C: Half-life (t1/2) of AMG 397 [Up to 6 months]

  50. Part 3A: Objective Response Rate (ORR) for Myelodysplastic Syndrome (MDS) Subjects [Up to 19 months]

    Response criteria per Revised International Working Group (IWG).

  51. Part 3A: Overall Survival (OS) [Up to 19 months]

  52. Part 3A: Progression-free survival (PFS) [Up to 19 months]

  53. Part 3A: Time to Response [Up to 19 months]

  54. Part 3A: Duration of Response (DoR) [Up to 19 months]

  55. Part 3A: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  56. Part 3A: Maximum Observed Concentration (Cmax) of Azacitidine [Pre-dose to 8 hours after infusion]

  57. Part 3A: Area Under the Concentration Time Curve (AUC) of AMG 397 [Up to 6 months]

  58. Part 3A: Area Under the Concentration Time Curve (AUC) of Azacitidine [Pre-dose to 8 hours after infusion]

  59. Part 3A: Clearance (CL) of AMG 397 [Up to 6 months]

  60. Part 3A: Clearance (CL) of Azacitidine [Pre-dose to 8 hours after infusion]

  61. Part 3A: Half-life (t1/2) of AMG 397 [Up to 6 months]

  62. Part 3A: Half-life (t1/2) of Azacitidine [Pre-dose to 8 hours after infusion]

  63. Part 3B: Objective Response Rate (ORR) for Acute Myeloid Leukemia (AML) Subjects [Up to 19 months]

    Response criteria per 2017 European LeukemiaNet (ELN) criteria.

  64. Part 3B: Progression-free survival (PFS) [Up to 19 months]

  65. Part 3B: Overall Survival (OS) [Up to 19 months]

  66. Part 3B: Time to Response [Up to 19 months]

  67. Part 3B: Duration of Response (DoR) [Up to 19 months]

  68. Part 3B: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  69. Part 3B: Maximum Observed Concentration (Cmax) of Azacitidine [Pre-dose to 8 hours after infusion]

  70. Part 3B: Area Under the Concentration Time Curve (AUC) of AMG 397 [Up to 6 months]

  71. Part 3B: Area Under the Concentration Time Curve (AUC) of Azacitidine [Pre-dose to 8 hours after infusion]

  72. Part 3B: Clearance (CL) of AMG 397 [Up to 6 months]

  73. Part 3B: Clearance (CL) of Azacitidine [Pre-dose to 8 hours after infusion]

  74. Part 3B: Half-life (t1/2) of AMG 397 [Up to 6 months]

  75. Part 3B: Half-life (t1/2) of Azacitidine [Pre-dose to 8 hours after infusion]

  76. Part 3C: Objective Response Rate (ORR) for Multiple Myeloma (MM) Subjects [Up to 19 months]

    Response criteria per International Myeloma Working Group - Uniform Response Criteria (IMWG-URC).

  77. Part 3C: Progression-free survival (PFS) [Up to 19 months]

  78. Part 3C: Overall Survival (OS) [Up to 19 months]

  79. Part 3C: Time to Response [Up to 19 months]

  80. Part 3C: Duration of Response (DoR) [Up to 19 months]

  81. Part 3C: Maximum Observed Concentration (Cmax) of AMG 397 [Up to 6 months]

  82. Part 3C: Maximum Observed Concentration (Cmax) of Dexamethasone [Pre-dose to 48 hours after infusion]

  83. Part 3C: Area Under the Concentration Time Curve (AUC) of AMG 397 [Up to 6 months]

  84. Part 3C: Area Under the Concentration Time Curve (AUC) of Dexamethasone [Pre-dose to 48 hours after infusion]

  85. Part 3C: Clearance (CL) of AMG 397 [Up to 6 months]

  86. Part 3C: Clearance (CL) of Dexamethasone [Pre-dose to 48 hours after infusion]

  87. Part 3C: Half-life (t1/2) of AMG 397 [Up to 6 months]

  88. Part 3C: Half-life (t1/2) of Dexamethasone [Pre-dose to 48 hours after infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Subject has provided informed consent prior to initiation of any study-specific activities/procedures

  • Age ≥ 18 years old

  • Pathologically-documented, definitively-diagnosed relapsed or refractory multiple myeloma (MM), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) and is intolerant to, or considered ineligible for available therapies known to provide clinical benefit

  • MM subjects only: Measurable disease per the International Myeloma Working Group (IMWG) response criteria (assessed within 21 days prior to enrollment), as indicated by one or more of the following: cytogenic risk factor: 1q21 amplification/gain, serum M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours. For Subjects who do not meet 1 of the 2 prior criteria: Serum Free Light Chain (sFLC) ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal sFLC ratio (< 0.26 or > 1.65) as per the IMWG response criteria

  • MM subjects only: Hematological function, as follows without transfusion or growth factor support within 2 weeks prior to study day 1: absolute neutrophil count ≥ 1.0 X 109/L, hemoglobin > 8 g/dL and platelet count ≥ 75 X 109/L

  • AML subjects only: Pathologically confirmed diagnosis of AML as defined by the World Health Organisation (WHO) Classification, more than 5% blasts in bone marrow and persisting or recurring following one or more treatment courses

  • MDS subjects only: pathologically confirmed diagnosis of MDS as defined by the WHO Classification, intermediate and high risk MDS and intolerant or refractory to HMA treatment

  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

  • Life expectancy of > 3 months, based on the opinion of the investigator

  • Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption.

  • Hepatic function, as follows:

  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN)

  • total bilirubin (TBL) < 1.5 X ULN (except subjects with Gilbert's syndrome)

  • Cardiac function, as follows:

  • Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion as determined by echocardiogram or multigated acquisition (MUGA) scan

  • no ECG findings representing a recent cardiac injury within 6 months before enrollment

  • Renal function as follows:

  • Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute calculated using the formula of Cockcroft and Gault [(140 - Age) × Mass (kg) / (72 × serum creatinine mg/dL)]. Multiply result by 0.85 if female

Exclusion Criteria:

Disease Related

  • Previously received an allogeneic stem cell transplant within 6 months of study day 1 OR having signs or symptoms of acute or chronic graft-versus-host disease

  • Autologous stem cell transplant < 90 days before enrollment

  • Candidates for stem cell transplant should have failed or are not considered eligible for either allogeneic and autologous transplant

Other Medical Conditions

  • History of other malignancy except:

  • Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician

  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

  • Adequately treated cervical carcinoma in situ without evidence of disease

  • Adequately treated breast ductal carcinoma in situ without evidence of disease

  • Prostatic intraepithelial neoplasia without evidence of prostate cancer

  • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ

  • Myocardial infarction within 6 months before 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 before enrollment

  • Uncontrollable active infection requiring intravenous anti-infective treatments within 1 week before enrollment

  • Known positive results for human immunodeficiency virus (HIV)

  • Active hepatitis B and C based on the following results: Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic, hepatitis B or recent acute hepatitis B), Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B. Positive Hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C

  • Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1, or to levels dictated in the eligibility criteria with the exception of grade 2peripheral neuropathy, alopecia or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 4 weeks prior to study day 1 may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor)

  • Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, retinoid therapy, or investigational agent or procedures) within 14 days of day 1

  • Prior systemic radiation therapy must have been completed at least 28 days before study day 1. Prior focal radiotherapy completed at 14 days before study day 1

  • Females of reproductive potential who are unwilling to practice acceptable methods of highly effective contraception while on study through 8 months after receiving the last dose of study drug. Males who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use a condom with or without spermicide while on study through 5 months after receiving the last dose of study drug if sexually active with a female of childbearing potential

  • Females who are lactating/breastfeeding or who plan to breastfeed while on study through 8 months after receiving the last dose of study drug

  • Females with a positive pregnancy test or planning to become pregnant while on study through 8 months after receiving the last dose of study drug

  • Males who are unwilling to abstain from sperm donation while on study through 8 months after receiving the last dose of study drug

  • History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

  • Use of any over-the-counter or prescription medications within 14 days or 5 half-lives (whichever is longer), prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor

  • Use of herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by the subject within 14 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor

  • Use of any known inhibitors of P-gp within 14 days or 5 half-lives (whichever is longer) or grapefruit juice or grapefruit containing products within 7 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor

  • Use of known CYP3A4 sensitive substrates, (with a narrow therapeutic window), within 14 days or 5 half-lives (whichever is longer) of the drug or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor

  • Use of known P-gp substrates (with a narrow therapeutic window) within 14 days or 5 half-lives (whichever is longer) prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor

  • Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, long term follow-up) to the best of the subject and investigator's knowledge

  • Known sensitivity to any of the products or component to be administered during dosing

  • MM subjects with any of the following criteria are excluded:

  • Multiple myeloma with IgM subtype

  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

  • Existing plasma cell leukemia

  • Waldenstrom's macroglobulinemia

  • Amyloidosis

  • AML subjects with the following criteria are excluded:

  • Circulating white blood cells > 25,000/μl. Hydroxyurea to control peripheral blood leukemic cell counts, within 24 hours of study day 1 is permitted

  • Promyelocytic leukemia

  • AML/MDS subjects fit for intensive salvage therapy

  • Subjects 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 (Covance)

  • Subjects with evidence of recent cardiac injury at screening based on creatine kinase-muscle/brain (CK-MB), N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP), and ECG assessments at screening

  • Subjects with MDS that are eligible for hematopoietic stem cell transplant (HSCT)

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of Alabama at BirminghamBirminghamAlabamaUnited States35249
2Mayo Clinic ArizonaPhoenixArizonaUnited States85054
3Mayo Clinic FloridaJacksonvilleFloridaUnited States32224
4University of Kansas Cancer CenterWestwoodKansasUnited States66205
5University of Maryland Greenebaum Cancer CenterBaltimoreMarylandUnited States21201
6Dana Farber Cancer InstituteBostonMassachusettsUnited States02215
7Mayo Clinic RochesterRochesterMinnesotaUnited States55905
8Washington UniversitySaint LouisMissouriUnited States63110
9Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263
10Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
11University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77030
12Froedtert and Med College WisconsinMilwaukeeWisconsinUnited States53226
13Royal Prince Alfred HospitalCamperdownNew South WalesAustralia2050
14Princess Alexandra HospitalWoolloongabbaQueenslandAustralia4102
15The Alfred HospitalMelbourneVictoriaAustralia3004
16Institut Paoli CalmettesMarseille Cedex 09France13272
17Institut Gustave RoussyVillejuifFrance94805
18Alexandra HospitalAthensGreece11528
19Azienda Socio Sanitaria Territoriale Papa Giovanni XXIIIBergamoItaly24127
20Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola MalpighiBolognaItaly40138
21Ogaki Municipal HospitalOgaki-shiGifuJapan503-8502

Sponsors and Collaborators

  • Amgen

Investigators

  • Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT03465540
Other Study ID Numbers:
  • 20170173
First Posted:
Mar 14, 2018
Last Update Posted:
Oct 11, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Amgen
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 11, 2021