Clinical Trials /

Study Evaluating AMG 424 in Subjects With Multiple Myeloma

NCT03445663

Description:

A multi-center Phase 1, First-in-Human study conducted in 2 Parts, testing AMG 424 in subjects with relapsed/ refractory multiple myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 20160445
  • NCT ID: NCT03445663

Conditions

  • Relapsed/ Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
AMG 424AMG 424

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
AMG 424ExperimentalComparison of different dosages of AMG 424
  • AMG 424

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0
Time Frame:12 Months
Safety Issue:
Description:Measure of Safety

Secondary Outcome Measures

Measure:Anti-tumor activity
Time Frame:48 Months
Safety Issue:
Description:Efficacy parameter measured by IMWG response criteria
Measure:Duration of Response
Time Frame:48 Months
Safety Issue:
Description:Measure of Response
Measure:Maximum concentration (Cmax) of AMG 424
Time Frame:12 Weeks
Safety Issue:
Description:Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Measure:Minimum concentration (Cmin) of AMG 424
Time Frame:12 Weeks
Safety Issue:
Description:Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Measure:Time of maximum concentration (Tmax) of AMG 424
Time Frame:12 Weeks
Safety Issue:
Description:Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Measure:Area under the concentration-time curve (AUC) of AMG 424
Time Frame:12 Weeks
Safety Issue:
Description:Characterize the pharmacokinetic (PK) profile following treatment with AMG 424
Measure:Time to progression
Time Frame:48 Months
Safety Issue:
Description:Measure of Response
Measure:Progression-Free Survival
Time Frame:48 Months
Safety Issue:
Description:Measure of Response
Measure:Overall Survival
Time Frame:48 Months
Safety Issue:
Description:Measure of Response

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • Relapsed/ Refractory Multiple Myeloma
  • Multiple Myeloma
  • Oncology/Hematology
  • Immunotherapy

Last Updated

November 26, 2019