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

Phase 1CompletedNCT02561962

Amgen42 enrolled

Overview

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

This is a first in human phase 1 multicenter open label study to evaluate the safety and tolerability of AMG 224 in subjects with relapsed or refractory multiple myeloma. The study will be conducted in 2 parts. Part 1 is the dose-exploration and part 2 is the dose-expansion. Study medication will be administered once every 3 weeks by intravenous (IV) infusion.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

AMG 224DRUG

Administered as an IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- 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% Exclusion Criteria: * 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

Locations (5)

Research Site

West Hollywood, California, United States

Research Site

Boston, Massachusetts, United States

Research Site

New York, New York, United States

Research Site

Houston, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

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

Cmax of AMG 224 conjugated antibody, total anti-BCMA antibody and total unconjugated DM1 was measured. DM1 is a semi-synthetic derivative of the ansamycin antibiotic, maytansine conjugated to the non-cleavable linker 4-\[N-maleimidomethyl\] cyclohexane-1-carboxylate conjugated to lysine residues in the antibody (MCC).

Data from ClinicalTrials.gov

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