Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. 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: NCT03836053
Recruitment Status : Not yet recruiting
First Posted : February 11, 2019
Last Update Posted : February 11, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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, and to expand on the dose determined as the Recommended Phase 2 Dose (RP2D).

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. Cohort 3 (Phase 2) will consist of 100 subjects dosed at 400 mcg/d. If the 600 mcg/d dose is determined to be superior, Phase 2 subjects may potentially receive this dose. 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
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

Phase 2 Primary Objectives:

Estimate ORR per IMWG response criteria

Phase 2 Key Secondary/Secondary Objectives:

Estimate DOR Evaluate the rate of MRD-negative disease at the time of CR Evaluate other measures of anti-myeloma activity: Time to response, PFS, OS, TFI, BOR Establish the safety/tolerability of AMG 420 in RRMM

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 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
Estimated Study Start Date : July 24, 2019
Estimated Primary Completion Date : March 24, 2021
Estimated Study Completion Date : March 23, 2025

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. Change in ECOG Performance Status from Baseline [ Time Frame: Day 1 to End of Treatment (up to 5 years) ]
    Percentage of patients with an improvement or degradation of ECOG performance status as compared to baseline


Secondary Outcome Measures :
  1. MRD Negativity [ Time Frame: Each course has a duration of 6 weeks, 4 weeks of continuous infusion of AMG 420 and 2 weeks break ]
    Number of subjects with minimal residual disease (MRD)-negativity at the time of Complete Response.



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

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:

    • 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 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
  3. ECOG performance status of less than or equal to 2
  4. Life expectancy of at least 3 months per PI judgement at screening
  5. 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)
  6. 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
  7. 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 ClinicalTrials.gov identifier (NCT number): NCT03836053


Contacts
Layout table for location contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen

Additional Information:
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03836053     History of Changes
Other Study ID Numbers: 20160370
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
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