Clinical trial NCT02561962: A Phase 1 Study in Subjects With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 1 First in Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 224 in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-09-28
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
timeFrame: Day 1 to Day 28
measure: Number of Participants With a Treatment-emergent Adverse Event (TEAE)
timeFrame: 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:
measure: Maximum Observed Concentration (Cmax) of AMG 224 Conjugated Antibody, Total Anti-B-cell Maturation Antigen (Anti-BCMA) Antibody, and Total Unconjugated DM1
timeFrame: 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)
measure: Minimum Observed Concentration (Cmin) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
timeFrame: 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)
measure: Area Under the Concentration-time Curve (AUC) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
timeFrame: 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)
measure: Clearance (CL) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
timeFrame: 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)
measure: Terminal Half-life (t1/2,z) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1
timeFrame: 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)
measure: Best Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
timeFrame: Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
measure: Time To Progression (TTP) According to IMWG-URC
timeFrame: Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
measure: Duration of Response (DOR) According to IMWG-URC
timeFrame: Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
measure: Number of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity
timeFrame: Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
measure: Number of Participants With Anti-AMG 224 Antibodies
timeFrame: Day 1 of Cycle 1 to up to the end of study visit; up to approximately 6 years
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: Research Site
state: California
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Prahran
country: Australia
facility: Research Site
state: Victoria
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
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.