Study Evaluating AMG 424 in Subjects With Multiple Myeloma

Relapsed/ Refractory Multiple Myeloma Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03445663
• Other study ID #: 20160445
• Status: Terminated
• Phase: Phase 1
• Start date: July 31, 2018
• Est. completion date: June 19, 2020

Study information

• Verified date: March 2023
• Source: Xencor, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: June 19, 2020
• Est. primary completion date: June 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/ Refractory Multiple Myeloma

Intervention

Drug:
• AMG 424
Subjects will receive IV infusions of AMG 424

Locations

Country	Name	City	State
Australia	Research Site	Camperdown	New South Wales
Australia	Research Site	Fitzroy	Victoria
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cleveland	Ohio
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	San Francisco	California
United States	Research Site	Seattle	Washington
United States	Research Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Xencor, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0	Measure of Safety	12 Months
Primary	Subject incidence of dose limiting toxicities (DLTs)	Measure of Safety	28 Days
Secondary	Anti-tumor activity	Efficacy parameter measured by IMWG response criteria	48 Months
Secondary	Duration of Response	Measure of Response	48 Months
Secondary	Maximum concentration (Cmax) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Secondary	Minimum concentration (Cmin) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Secondary	Time of maximum concentration (Tmax) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Secondary	Area under the concentration-time curve (AUC) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Secondary	Time to progression	Measure of Response	48 Months
Secondary	Progression-Free Survival	Measure of Response	48 Months
Secondary	Overall Survival	Measure of Response	48 Months

External Links

•   AmgenTrials clinical trials website