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Assessment of AMG 420 in Subjects With Relapsed and/or Refractory Multiple Myeloma (AMG420)

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. Read our disclaimer for details. Identifier: NCT03836053
Recruitment Status : Completed
First Posted : February 11, 2019
Last Update Posted : May 17, 2022
Information provided by (Responsible Party):

Brief Summary:
To confirm the maximum tolerated dose (MTD) from the BI 836909 trial of 400 mcg/d, given as 28-day continuous intravenous infusion in patients with relapsed and/or refractory multiple myeloma, to test the 600 mcg/d dose, given as a 28-day continuous iV infusion.

Condition or disease Intervention/treatment Phase
Relapsed and/or Refractory Multiple Myeloma Drug: AMG 420 Phase 1

Detailed Description:
Cohort 1 will consist of 10 subjects dosed at 400 mcg/d. Cohort 2 will consist of 10 subjects dosed at 600 mcg/d. All doses will be given as a 28-day continuous IV infusion, followed by a 2 week treatment-free interval, until subject experiences disease progression as per International Myeloma Working Group (IMWG) criteria.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Phase 1b Primary objective Establish the safety and tolerability of AMG 420 at dose levels of 400 mcg/day and 600 mcg/day in subjects with relapsed and/or refractory multiple myeloma (RRMM)

Phase 1b Key Secondary/Secondary objectives:

Estimate overall response rate (ORR) and duration of response (DOR) Evaluate the rate of minimal residual disease (MRD)-negativity at the time of CR Establish the safety and tolerability of AMG 420 in subjects with extramedullary relapsed MM Characterize the PK of AMG 420 when administered as 4-week continuous IV infusion Evaluate other measures of anti-myeloma activity of AMG 420: Time to response, PFS, OS, TFI, BOR

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Multicenter, Open-label, Expansion Study to Assess the Safety and Efficacy of AMG 420 as Monotherapy in Subjects With Relapsed and/or Refractory Multiple Myeloma
Actual Study Start Date : March 4, 2019
Actual Primary Completion Date : April 21, 2022
Actual Study Completion Date : April 21, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: AMG 420
Single Arm Design
Drug: AMG 420
28 day continuous Intravenous infusion of either 400 mcg/d or 600 mcg/d followed by 2 treatment free weeks

Primary Outcome Measures :
  1. Subject incidence of dose-limiting toxicities [ Time Frame: 4 weeks ]
    Evaluate incidence of subjects experiencing dose-limiting toxicities

  2. Subject incidence of treatment emergent adverse events [ Time Frame: 4 weeks ]
    Evaluate incidence of subjects experiencing treatment emergent adverse events

  3. Subject incidence of treatment related adverse events [ Time Frame: 4 weeks ]
    Evaluate incidence of subjects experiencing treatment related adverse events

  4. Subject incidence of changes in vital signs [ Time Frame: 4 weeks ]
    Evaluate incidence of subjects experiencing changes in vital signs

  5. Subject Incidence of Changes in ECGs [ Time Frame: 4 weeks ]
    Evaluate incidence of subjects experiencing changes in ECGs

  6. Subject incidence of Changes in clinical laboratory tests [ Time Frame: 4 weeks ]
    Evaluate incidence of subjects experiencing changes in clinical laboratory tests

Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 6 months ]
    Evaluate the rate of subjects responding to treatment with AMG 420

  2. Duration of Response [ Time Frame: 6 months ]
    Evaluate the duration of subject responses to treatment with AMG 420

  3. Minimal Residual Disease negativity at the time of CR [ Time Frame: 6 months ]
    Evaluate MRD negativity at the time a subject achieves complete response

  4. Half-life [ Time Frame: 4 weeks ]
    Half life of AMG 420

  5. Time to response [ Time Frame: 6 months ]
    Time to response of AMG 420

  6. Clearance [ Time Frame: 6 months ]
    Clearance of AMG 420

  7. Apparent Css [ Time Frame: 6 months ]
    Apparent Css of AMG 420

  8. Progression Free Survival (PFS) [ Time Frame: 6 months ]
    PFS of AMG 420

  9. Overall Survival [ Time Frame: 6 months ]
    OS of of AMG 420

  10. Best Overall Response [ Time Frame: 6 months ]
    BOR of AMG 420

  11. Treatment-free Interval [ Time Frame: 6 months ]
    TFI of AMG 420

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  1. Subject has provided informed consent prior to initiation of any study specific activities/procedures
  2. Multiple myeloma meeting the following criteria:
  3. Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following: Relapsed after 3 or more lines of prior therapy that must include a proteasome inhibitors (PI), an immunomodulators (IMiD), and a CD38-directed monoclonal antibody in any order during the course of treatment OR refractory to a PI, IMiD, and CD38-directed monoclonal antibody.

    -Measurable disease, defined by 1 or more of the following at time of screening: 1) serum M-protein > 0.5 g/dL measured by serum protein electrophoresis (SPEP); 2) urinary M-protein excretion > 200 mg/24 hours; 3) Involved serum free light chain (sFLC ) measurement > 10 mg/dL, provided that the sFLC ratio is abnormal (<0.26 or >1.65) as per IMWG response criteria

  4. . ECOG performance status of less than or equal to 2
  5. Life expectancy of at least 3 months per PI judgement at screening
  6. Hematological function without transfusion support (within 7 days from screening assessment) as follows:

    • ANC ≥ 1.0 x 10^9/L (without growth factor support)
    • platelet count ≥ 25 x 10^9/L (without transfusions)
    • hemoglobin ≥ 7.0 g/dL (transfusions permitted no later than 48 hours before screening)
  7. Renal function as follows: calculated or measured creatinine clearance ≥30 mL/min using the Cockcroft-Gault equation or via 24-hour urine collection with plasma and urine creatinine concentrations, respectively
  8. Hepatic function as follows: AST and ALT < 3x upper limit of normal (ULN); TBIL <1.5 x ULN (unless considered due to Gilbert's syndrome)

Key Exclusion Criteria:

  1. Known central nervous system involvement by multiple myeloma
  2. Evidence of primary or secondary plasma cell leukemia at the time of screening
  3. Waldenstrom's macroglobulinemia
  4. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 5.0 grade 1 or to levels dictated in the eligibility criteria with the exception of grade 2 peripheral neuropathy, alopecia, or toxicities from prior anticancer therapy that are considered irreversible (defined as having been present and stable for > 4 weeks) which may be allowed if they are not otherwise described in the exclusion criteria and there is agreement to allow by the PI and Amgen medical monitor
  5. History of other malignancy within the past 3 years, with the following exceptions: 1. malignancy treated with curative intent and with no known active disease present for ≥ 1 year before enrollment and felt to be at low risk for recurrence by the treating physician; 2. adequately-treated non-melanoma skin cancer or lentigo maligna without evidence of disease; 3. adequately-treated cervical carcinoma in situ without evidence of disease; 4. breast ductal carcinoma in situ with full surgical resection (ie, negative margins) and without evidence of disease; 5. prostate cancer with a Gleason score < 6 with undetectable PSA over 12 months; 6. treated medullary or papillary thyroid cancer; 7. adequately-treated urothelial papillary noninvasive carcinoma or carcinoma in situ; similar neoplastic conditions with an expectation of > 95% five-year disease-free survival; 8. see exclusion criterion # 2 for exclusion of subjects with evidence of primary or secondary plasma cell leukemia at the time of screening
  6. Known history of amyloidosis
  7. Current or known history of autoimmune diseases requiring systemic treatment in past 5 years except vitiligo, resolved childhood asthma/atopy, or subjects with history of hypothyroidism after completing treatment for autoimmune thyroid disease, stable on hormone replacement therapy.
  8. Clinically not-controlled chronic or ongoing infectious disease requiring treatment at the time of study day 1 or within the 14 days before study day 1
  9. Symptomatic peripheral sensory or motor neuropathy of grade ≥3
  10. History or presence of clinically relevant central nervous system (CNS) pathology as uncontrolled epilepsy or seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
  11. Active hepatitis B and C based on the following results: a) Positive for HepBsAg; b) Negative HepBsAg and positive for hepatitis B core antibody; c) Positive Hepatitis C virus antibody (HepCAb)
  12. Known or suspected HIV infection or subjects who are HIV seropositive
  13. Baseline ECG QTc > 470 msec (applying Fridericia correction)
  14. Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the following: a) received the transplant within 6 months prior to study day 1; b) received immunosuppressive therapy within the last 3 months prior to study day 1; c) any active acute graft versus host disease (GvHD), grade 2 to 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment; d) any systemic therapy against GvHD within 2 weeks prior to start of investigational product treatment
  15. Autologous stem cell transplantation < 90 days prior to study day 1
  16. Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1
  17. Last anticancer treatment < 2 weeks prior to study day 1
  18. Last treatment with a therapeutic antibody less than 4 weeks prior to study day 1
  19. Systemic radiation therapy within 28 days prior to study day 1. Focal radiotherapy within 14 days prior to study day 1.
  20. Major surgery defined as surgery requiring general anesthesia with endotracheal intubation within 28 days prior to study day 1, unless discussed with and eligibility approved by Amgen medical monitor
  21. Prior treatment with any drug that specifically targets BCMA on tumor cells (eg, other bi-specific antibody constructs, antibody drug conjugates, or CAR T-cells, except for subjects who were previously treated with AMG 420 in this study and who are candidates for second-course treatment
  22. Treatment with medications known to cause QTc interval prolongation within the washout periods described in Section 12.10 unless approved by the Amgen medical monitor
  23. Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
  24. History or evidence of any other clinically-significant disorder, condition, or disease (eg, symptomatic congestive heart failure, unstable angina pectoris,cardiac arrhythmia requiring therapy at time of screening) with the exception of those outlined above that, in the opinion of the investigator or Amgen medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

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 identifier (NCT number): NCT03836053

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United States, Illinois
Advocate Lutheran General Hospital
Park Ridge, Illinois, United States, 60068
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
Australia, New South Wales
St Vincents Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
Australia, Victoria
St Vincents Hospital Melbourne
Fitzroy, VIC, Victoria, Australia, 3065
Centres Hospitaliers Jolimont - Hopital de Jolimont
Haine Saint Paul - La Louviere, Belgium, 7100
Centre Hospitalier Universitaire Dinant Godinne - Universite Catholique de Louvain Namur
Yvoir, Belgium, 5530
National Hospital Organization Okayama Medical Center
Okayama-shi, Okayama, Japan, 701-1192
Kantonsspital St Gallen
St. Gallen, Switzerland, 9007
Sponsors and Collaborators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen Identifier: NCT03836053    
Other Study ID Numbers: 20160370
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: May 17, 2022
Last Verified: May 2022
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.

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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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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases