Description:
A multi-center Phase 1, First-in-Human study conducted in 2 Parts, testing AMG 424 in
subjects with relapsed/ refractory multiple myeloma.
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
Drug | Synonyms | Arms |
---|
AMG 424 | | AMG 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
Name | Type | Description | Interventions |
---|
AMG 424 | Experimental | Comparison of different dosages of 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: | Terminated |
Lead Sponsor: | Amgen |
Trial Keywords
- Relapsed/ Refractory Multiple Myeloma
- Multiple Myeloma
- Oncology/Hematology
- Immunotherapy
Last Updated
May 10, 2021