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Study Evaluating AMG 424 in Subjects With Multiple Myeloma

Primary Purpose

Relapsed/ Refractory Multiple Myeloma

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AMG 424
Sponsored by
Xencor, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/ Refractory Multiple Myeloma focused on measuring Relapsed/ Refractory Multiple Myeloma, Multiple Myeloma, Oncology/Hematology, Immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Multiple myeloma meeting the following criteria:

  • Pathologically-documented diagnosis of multiple myeloma that has relapsed after at least two prior lines of therapy that must include a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and, where approved and available, anti-CD38 therapy in any order OR that is refractory to PI, IMiD, and anti-CD38 therapy.

    ◾Subjects who could not tolerate a PI, IMiDs, or a CD38-directed therapeutic antibody due to unacceptable toxicities are eligible to enroll in the study.

  • Measurable disease as per IMWG response criteria
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

Exclusion Criteria:

  • Known central nervous system involvement by multiple myeloma

  • Previously received allogeneic stem cell transplant and one or more of the following:

    • received the transplant < 6 months prior to study Day 1
    • received immunosuppressive therapy < 3 months prior to study Day 1
    • any active acute graft versus host disease (GvHD), grade 2- 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment
    • any systemic therapy against GvHD < 2 weeks prior to study Day 1
  • Autologous stem cell transplantation less than 90 days prior to study day 1
  • Multiple myeloma with IgM subtype
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Evidence of primary or secondary plasma cell leukemia at the time of screening
  • Waldenstrom's macroglobulinemia
  • Amyloidosis
  • Dexamethasone at cumulative doses of greater than 160 mg or equivalent <3 weeks prior to study Day 1 is not allowed. Use of topical or inhaled steroids is acceptable
  • Anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study Day 1
  • Treatment with a therapeutic antibody targeting CD38 < 12 weeks prior to study Day 1
  • Systemic radiation therapy or major surgery < 28 days prior to study Day 1 as well as focal radiotherapy < 14 days prior to study Day 1.
  • Major surgery within 28 days prior to study Day 1

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AMG 424

Arm Description

Comparison of different dosages of AMG 424

Outcomes

Primary Outcome Measures

Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0
Measure of Safety
Subject incidence of dose limiting toxicities (DLTs)
Measure of Safety

Secondary Outcome Measures

Anti-tumor activity
Efficacy parameter measured by IMWG response criteria
Duration of Response
Measure of Response
Maximum concentration (Cmax) of AMG 424
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Minimum concentration (Cmin) of AMG 424
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Time of maximum concentration (Tmax) of AMG 424
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Area under the concentration-time curve (AUC) of AMG 424
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Time to progression
Measure of Response
Progression-Free Survival
Measure of Response
Overall Survival
Measure of Response

Full Information

First Posted
February 1, 2018
Last Updated
March 3, 2023
Sponsor
Xencor, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03445663
Brief Title
Study Evaluating AMG 424 in Subjects With Multiple Myeloma
Official Title
A Phase 1, First-in-Human, Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 424 in Subjects With Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Previous sponsor business decision not to proceed with the AMG 424 asset.
Study Start Date
July 31, 2018 (Actual)
Primary Completion Date
June 19, 2020 (Actual)
Study Completion Date
June 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xencor, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A multi-center Phase 1, First-in-Human study conducted in 2 Parts, testing AMG 424 in subjects with relapsed/ refractory multiple myeloma.
Detailed Description
Part 1 of the study is dose evaluating and aimed at assessing the safety and tolerability of AMG 424 while determining the maximum tolerated dose (MTD) and/or biologically active dose in subjects with relapsed/ refractory multiple myeloma. Part 2 of the study will further evaluate safety and tolerability of the AMG 424 MTD dose determined in Part 1, in groups of subjects with relapsed/ refractory multiple myeloma that include those with high or low cytogenetic risk.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/ Refractory Multiple Myeloma
Keywords
Relapsed/ Refractory Multiple Myeloma, Multiple Myeloma, Oncology/Hematology, Immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AMG 424
Arm Type
Experimental
Arm Description
Comparison of different dosages of AMG 424
Intervention Type
Drug
Intervention Name(s)
AMG 424
Intervention Description
Subjects will receive IV infusions of AMG 424
Primary Outcome Measure Information:
Title
Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0
Description
Measure of Safety
Time Frame
12 Months
Title
Subject incidence of dose limiting toxicities (DLTs)
Description
Measure of Safety
Time Frame
28 Days
Secondary Outcome Measure Information:
Title
Anti-tumor activity
Description
Efficacy parameter measured by IMWG response criteria
Time Frame
48 Months
Title
Duration of Response
Description
Measure of Response
Time Frame
48 Months
Title
Maximum concentration (Cmax) of AMG 424
Description
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Time Frame
12 Weeks
Title
Minimum concentration (Cmin) of AMG 424
Description
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Time Frame
12 Weeks
Title
Time of maximum concentration (Tmax) of AMG 424
Description
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Time Frame
12 Weeks
Title
Area under the concentration-time curve (AUC) of AMG 424
Description
Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Time Frame
12 Weeks
Title
Time to progression
Description
Measure of Response
Time Frame
48 Months
Title
Progression-Free Survival
Description
Measure of Response
Time Frame
48 Months
Title
Overall Survival
Description
Measure of Response
Time Frame
48 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Multiple myeloma meeting the following criteria: Pathologically-documented diagnosis of multiple myeloma that has relapsed after at least two prior lines of therapy that must include a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and, where approved and available, anti-CD38 therapy in any order OR that is refractory to PI, IMiD, and anti-CD38 therapy. ◾Subjects who could not tolerate a PI, IMiDs, or a CD38-directed therapeutic antibody due to unacceptable toxicities are eligible to enroll in the study. Measurable disease as per IMWG response criteria Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 Exclusion Criteria: Known central nervous system involvement by multiple myeloma Previously received allogeneic stem cell transplant and one or more of the following: received the transplant < 6 months prior to study Day 1 received immunosuppressive therapy < 3 months prior to study Day 1 any active acute graft versus host disease (GvHD), grade 2- 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment any systemic therapy against GvHD < 2 weeks prior to study Day 1 Autologous stem cell transplantation less than 90 days prior to study day 1 Multiple myeloma with IgM subtype POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) Evidence of primary or secondary plasma cell leukemia at the time of screening Waldenstrom's macroglobulinemia Amyloidosis Dexamethasone at cumulative doses of greater than 160 mg or equivalent <3 weeks prior to study Day 1 is not allowed. Use of topical or inhaled steroids is acceptable Anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study Day 1 Treatment with a therapeutic antibody targeting CD38 < 12 weeks prior to study Day 1 Systemic radiation therapy or major surgery < 28 days prior to study Day 1 as well as focal radiotherapy < 14 days prior to study Day 1. Major surgery within 28 days prior to study Day 1
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Research Site
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Research Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Research Site
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Research Site
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

Study Evaluating AMG 424 in Subjects With Multiple Myeloma

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