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

Amgen

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: AMG 224

Study type: Interventional

Funder types: Industry

Identifiers

NCT02561962

20130314

Details and patient eligibility

About

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

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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42 participants in 9 patient groups

Dose Exploration: AMG 224 Dose A

Experimental group

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.

Treatment:

Drug: AMG 224

Dose Exploration: AMG 224 Dose B

Experimental group

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.

Treatment:

Drug: AMG 224

Dose Exploration: AMG 224 Dose C

Experimental group

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.

Treatment:

Drug: AMG 224

Dose Exploration: AMG 224 Dose D

Experimental group

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.

Treatment:

Drug: AMG 224

Dose Exploration: AMG 224 Dose E

Experimental group

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.

Treatment:

Drug: AMG 224

Dose Exploration: AMG 224 Dose F

Experimental group

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.

Treatment:

Drug: AMG 224

Dose Exploration: AMG 224 Dose G

Experimental group

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.

Treatment:

Drug: AMG 224

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

Experimental group

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.

Treatment:

Drug: AMG 224

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

Experimental group

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.

Treatment:

Drug: AMG 224