A Phase 1 Study in Subjects With Relapsed or Refractory Multiple Myeloma

NCT02561962 | Completed Phase 1 Results

• 1 other identifier: 20130314
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a first in human phase 1 multicenter open label study in subjects with relapsed or refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)

  Adverse events, including DLTs, were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be possibly related to AMG 224: Hematological: * Grade 4 neutropenia lasting \> 7 days * Grade 3 or 4 neutropenia with fever \> 38.5°C * Grade 3 thrombocytopenia with ≥ Grade 2 hemorrhage * Grade 4 thrombocytopenia lasting \> 7 days * Grade 3 anemia with symptoms or required intervention * Grade 4 anemia * Lymphopenia is not considered a DLT Non-hematological: * ≥ Grade 3 nausea, vomiting or diarrhea persisting \> 3 days despite optimal medical support * Grade 3 fatigue persisting \> 7 days * ≥ Grade 3 acute kidney injury lasting \> 3 days * Elevation of aspartate aminotransferase or alanine aminotransferase \>3x to \>8x upper limit of normal (ULT) dependent on criteria * Total bilirubin \> 3x ULN Participants meeting the criteria for Hy's Law case were considered to have a DLT.

  Day 1 to Day 28

• Number of Participants With a Treatment-emergent Adverse Event (TEAE)

  An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that occurred after receiving at least 1 dose of treatment. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in ECGs, vital signs, physical examination with a neurologic assessment and clinical laboratory tests were recorded as TEAEs.

  Day 1 of Cycle 1 to up to the end of Cycle 4, where each cycle is 3 weeks; up to 12 weeks.

Secondary Outcomes (10)

• Maximum Observed Concentration (Cmax) of AMG 224 Conjugated Antibody, Total Anti-B-cell Maturation Antigen (Anti-BCMA) Antibody, and Total Unconjugated DM1

  AMG 224 and anti-BCMA antibody: pre-dose, 0.5 hours, end of infusion (EOI), 4 hours, 24 hours, 96 hours, 168 hours, and 336 hours post-dose (Cycles 1 + 2); DM1: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, and 96 hours post-dose (Cycles 1 + 2)

• Minimum Observed Concentration (Cmin) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1

  AMG 224 and anti-BCMA antibody: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, 96 hours, 168 hours, and 336 hours post-dose (Cycles 1 + 2); DM1: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, and 96 hours post-dose (Cycles 1 + 2)

• Area Under the Concentration-time Curve (AUC) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1

  AMG 224 and anti-BCMA antibody: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, 96 hours, 168 hours, and 336 hours post-dose (Cycle 1 + 2); DM1: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, and 96 hours post-dose (Cycles 1 + 2)

• Clearance (CL) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1

  AMG 224 and anti-BCMA antibody: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, 96 hours, 168 hours, and 336 hours post-dose (Cycles 1 + 2); DM1: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, and 96 hours post-dose (Cycles 1 + 2)

• Terminal Half-life (t1/2,z) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1

  AMG 224 and anti-BCMA antibody: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, 96 hours, 168 hours, and 336 hours post-dose (Cycles 1 + 2); DM1: pre-dose, 0.5 hours, EOI, 4 hours, 24 hours, and 96 hours post-dose (Cycles 1 + 2)

Study Arms (9)

Dose Exploration: AMG 224 Dose A

EXPERIMENTAL

Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Exploration: AMG 224 Dose B

EXPERIMENTAL

Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Exploration: AMG 224 Dose C

EXPERIMENTAL

Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Exploration: AMG 224 Dose D

EXPERIMENTAL

Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Exploration: AMG 224 Dose E

EXPERIMENTAL

Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Exploration: AMG 224 Dose F

EXPERIMENTAL

Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Exploration: AMG 224 Dose G

EXPERIMENTAL

Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Expansion: AMG 224 Dose H + prior CD38 targeting antibody treatment

EXPERIMENTAL

Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose \[MTD\] based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Dose Expansion: AMG 224 Dose H + no prior CD38 targeting antibody treatment

EXPERIMENTAL

Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224

Interventions

AMG 224 DRUG

Administered as an IV infusion.

Dose Expansion: AMG 224 Dose H + no prior CD38 targeting antibody treatment; Dose Expansion: AMG 224 Dose H + prior CD38 targeting antibody treatment; Dose Exploration: AMG 224 Dose A; Dose Exploration: AMG 224 Dose B; Dose Exploration: AMG 224 Dose C; Dose Exploration: AMG 224 Dose D; Dose Exploration: AMG 224 Dose E; Dose Exploration: AMG 224 Dose F; Dose Exploration: AMG 224 Dose G

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Pathologically documented,multiple myeloma relapsed or refractory progressive disease after at least 3 lines of therapy for multiple myeloma.
• Prior therapeutic treatment or regimens must include proteasome inhibitors (e.g. bortezomib) and immunomodulatory drugs (e.g. lenalidomide).
• Willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).
• Measurable disease per the International Myeloma Working Group (IMWG) response criteria
• Hematological function, as follows, without transfusion support:
• Absolute neutrophil count ≥ 1.0 X 10\^9/L,
• Platelet count ≥ 75 X 10\^9/L (in patients with \< 50% of bone marrow nucleated cells were plasma cells) or ≥ 50 X 10\^9/L (in patients with ≥ 50% of bone marrow nucleated cells were plasma cells) without transfusion or growth factor support
• Hemoglobin \> 8 g/dL (\> 80 g/L)
• Adequate renal and hepatic function
• Left ventricular ejection fraction (LVEF) \> 50%

You may not qualify if:

• Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study
• Autologous stem cell transplant less than 90 days prior to study day 1
• Multiple myeloma with IgM subtype
• POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome, Plasma cell leukemia, Waldenstrom's macroglobulinemia or Amyloidosis
• Glucocorticoid therapy (prednisone \> 30 mg/day or equivalent) within 7 days prior to study day
• Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association \> class II)
• A baseline ECG QTcF \> 470 msec
• Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 28 days prior to study day 1

Sponsors & Collaborators

• Amgen: lead

Study Sites (5)

Research Site

West Hollywood, California, 90069, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Prahran, Victoria, 3181, Australia

Location

Related Publications (1)

• Lee HC, Raje NS, Landgren O, Upreti VV, Wang J, Avilion AA, Hu X, Rasmussen E, Ngarmchamnanrith G, Fujii H, Spencer A. Phase 1 study of the anti-BCMA antibody-drug conjugate AMG 224 in patients with relapsed/refractory multiple myeloma. Leukemia. 2021 Jan;35(1):255-258. doi: 10.1038/s41375-020-0834-9. Epub 2020 Apr 21. No abstract available.

  PMID: 32317775 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2015
• First Posted: September 28, 2015
• Study Start: November 20, 2015
• Primary Completion: November 30, 2018
• Study Completion: April 21, 2022
• Last Updated: February 1, 2024
• Results First Posted: October 7, 2021

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (4); AU (1)