NCT02561962 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2024-02-01

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Best Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)

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outcome · POSTED

Time To Progression (TTP) According to IMWG-URC

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outcome · POSTED

Duration of Response (DOR) According to IMWG-URC

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outcome · POSTED

Number of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity

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outcome · POSTED

Number of Participants With Anti-AMG 224 Antibodies

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: AMG 224
label
Dose Exploration: AMG 224 Dose A
type
EXPERIMENTAL
description
Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
intervention Names
Drug: AMG 224
label
Dose Exploration: AMG 224 Dose B
type
EXPERIMENTAL
description
Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
intervention Names
Drug: AMG 224
label
Dose Exploration: AMG 224 Dose C
type
EXPERIMENTAL
description
Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
intervention Names
Drug: AMG 224
label
Dose Exploration: AMG 224 Dose D
type
EXPERIMENTAL
description
Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
intervention Names
Drug: AMG 224
label
Dose Exploration: AMG 224 Dose E
type
EXPERIMENTAL
description
Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
intervention Names
Drug: AMG 224
label
Dose Exploration: AMG 224 Dose F
type
EXPERIMENTAL
description
Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
intervention Names
Drug: AMG 224
label
Dose Exploration: AMG 224 Dose G
type
EXPERIMENTAL
description
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.
intervention Names
Drug: AMG 224
label
Dose Expansion: AMG 224 Dose H + prior CD38 targeting antibody treatment
type
EXPERIMENTAL
description
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.
intervention Names
Drug: AMG 224
label
Dose Expansion: AMG 224 Dose H + no prior CD38 targeting antibody treatment
type
EXPERIMENTAL

interventions

arm Group Labels
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
description
Administered as an IV infusion.
name
AMG 224
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 42
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
time Frame
Day 1 to Day 28
description
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.
measure
Number of Participants With a Treatment-emergent Adverse Event (TEAE)
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

description
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).
measure
Maximum Observed Concentration (Cmax) of AMG 224 Conjugated Antibody, Total Anti-B-cell Maturation Antigen (Anti-BCMA) Antibody, and Total Unconjugated DM1
time Frame
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)
description
Cmin of AMG 224 conjugated antibody, total anti-BCMA antibody and total unconjugated DM1 was measured.
measure
Minimum Observed Concentration (Cmin) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
time Frame
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)
description
AUC from time zero to 3 weeks (AUC(3 weeks)) was determined for AMG 224 conjugated antibody and total anti-BCMA antibody, and AUC from time zero to 96 hours (AUC(0-96hr)) was determined for DM1.
measure
Area Under the Concentration-time Curve (AUC) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
time Frame
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)
description
CL of AMG 224 conjugated antibody, total anti-BCMA antibody and total unconjugated DM1 was determined.
measure
Clearance (CL) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
time Frame
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)
description
The t1/2,z of AMG 224 conjugated antibody, total anti-BCMA antibody and total unconjugated DM1 was measured.
measure
Terminal Half-life (t1/2,z) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
time Frame
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)
description
BOR was the best observed post baseline disease response per IMWG-URC: Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to \< 200 mg/24-h. Minor Response (MR): 25-49% reduction of serum M-protein and 50-89% in 24-h urinary M-protein, exceeding 200 mg/24-h. Stable Disease (SD): Not meeting criteria for CR, VGPR, PR or Progressive Disease (PD). PD: ≥ 25% increase in serum or urine M-component, development of new or increased size of existing bone lesions or soft tissue plasmacytomas, hypercalcemia attributed to the plasma cell proliferative disorder.
measure
Best Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
time Frame
Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
description
TTP was the time from the first administration of AMG 224 to the first objective assessment of disease progression as per IMWG-URC or deaths or if applicable date of censoring. The median TTP was estimated using the Kaplan-Meier method
measure
Time To Progression (TTP) According to IMWG-URC
time Frame
Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
description
DOR was defined as the time between the date of the first observation indicating an objective response as PR (or better) through to the subsequent date of disease progression as classified by the IMWG-URC for Multiple Myeloma or death or where applicable date of censoring. The median DOR was estimated using the Kaplan-Meier method.
measure
Duration of Response (DOR) According to IMWG-URC
time Frame
Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
description
MRD negative was defined as a tumor load of less than 1 clonal cell in 10\^5 normal cells (as determined by flow cytometry).
measure
Number of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity
time Frame
Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
description
The number of participants who tested positive for pre-existing binding antibodies prior to exposure to AMG 224 and who tested positive for anti-AMG 224 binding antibodies after dosing with AMG 224 are presented. Participants with transient post-baseline results were binding antibody positive post-baseline with a negative or no result at baseline and a negative result at the participant's last timepoint tested.
measure
Number of Participants With Anti-AMG 224 Antibodies
time Frame
Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years

Full study description

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

Source references

references

citation
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
type
BACKGROUND