Relapsed or Refractory Multiple Myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: AMG420
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: not available
Current Sponsor code: AMG 420
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject has provided informed consent prior to initiation of any study specific activities/procedures. Age = 18 years at the time of the signing of informed consent. Multiple myeloma meeting the following criteria: •Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following: -Relapsed after = 3 lines of prior therapy that must include a PI, an IMiD, and a CD38-directed monoclonal antibody in any order during the course of treatment OR refractory to PI, IMiD, and CD38-directed monoclonal antibody. •Measurable disease, defined by 1 or more of the following at time of screening: -serum M-protein > 0.5 g/dL measured by serum protein electrophoresis (SPEP) -urinary M-protein excretion > 200 mg/24 hours -Involved sFLC measurement > 10 mg/dL, provided that the sFLC ratio is abnormal ( 1.65) as per IMWG response criteria. Eastern Cooperative Oncology Group (ECOG) performance status of = 2. Life expectancy of at least 3 months as per investigator`s judgment at time of screening. Hematological function without transfusion support (within 7 days from screening assessment) as follows: •ANC = 1.0 x 109/L (without growth factor support) •platelet count = 25 x 109/L (without transfusions) •hemoglobin = 7.0 g/dL (transfusions permitted no later than 48 hours before screening). Renal function as follows: • calculated or measured creatinine clearance = 30 mL/min using the Cockcroft-Gault equation or via 24-hour urine collection with plasma and urine creatinine concentrations, respectively. Hepatic function as follows: •aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: Disease Related: Known central nervous system involvement by multiple myeloma. Evidence of primary or secondary plasma cell leukemia at the time of screening. Waldenstrom’s macroglobulinemia. Unresolved toxicities from prior anticancer therapy. Other Medical Conditions History of other malignancy within the past 3 years, with the following exceptions: •malignancy treated with curative intent and with no known active disease present for = 1 year before enrollment and felt to be at low risk for recurrence by the treating physician •adequately-treated non-melanoma skin cancer or lentigo maligna without evidence of disease •adequately-treated cervical carcinoma in situ without evidence of disease •breast ductal carcinoma in situ with full surgical resection (ie, negative margins) and without evidence of disease •prostate cancer with a Gleason score 95% five-year disease-free survival • see exclusion criterion 202 (Evidence of primary or secondary plasma cell leukemia at the time of screening) for exclusion of subjects with evidence of primary or secondary plasma cell leukemia at the time of screening. Known history of amyloidosis. Current or known history of autoimmune diseases requiring systemic treatment in past 5 years except vitiligo, resolved childhood asthma/atopy, or subjects with history of hypothyroidism after completing treatment for autoimmune thyroid disease, stable on hormone replacement therapy. Clinically not-controlled chronic or ongoing infectious disease requiring treatment at the time of study day 1 or within the 14 days before study day 1 Symptomatic peripheral sensory or motor neuropathy of grade = 3. History or presence of clinically relevant central nervous system (CNS) pathology as uncontrolled epilepsy or seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, and psychosis. Active hepatitis B and C based on the following results: •Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B). •Negative HepBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B. •Positive Hepatitis C virus antibody (HepCAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C. Known or suspected HIV infection or subjects who are HIV seropositive. Baseline ECG QTc > 470 msec (applying Fridericia correction), defined as the average of individual baseline ECGs. Prior/Concomitant Therapy Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the following: •received
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b • Establish the safety and tolerability of AMG 420 at dose levels of 400 µg/day and 600 µg/day in subjects with relapsed and/or refractory multiple myeloma (RRMM). Phase 2 • Estimate overall response rate (ORR) per IMWG response criteria (stringent complete response [sCR], complete response [CR], very good partial response [VGPR], partial response [PR]) in subjects with RRMM. ; Secondary Objective: Phase 1b Key Secondary • Estimate ORR and duration of response (DOR) of AMG 420 in subjects with RRMM • Evaluate the rate of minimal residual disease (MRD)-negativity at the time of CR Secondary • Establish the safety and tolerability of AMG 420 in subjects with extramedullary relapsed multiple myeloma •Characterize the pharmacokinetics of AMG 420 when administered as 4- week continuous intravenous (cIV) infusion •Evaluate other measures of anti-myeloma activity of AMG 420 in subjects with RRMM: -Time to response -Progression-free survival (PFS) -Overall survival (OS) -Treatment-free interval (TFI) -Best overall response (BOR) Phase 2 Key Secondary • Estimate DOR of AMG 420 in subjects with RRMM • Evaluate the rate of MRD-negative disease at the time of CR Secondary • Evaluate other measures of anti-myeloma activity of AMG 420 in subjects with RRMM: -Time to response -PFS -OS -TFI -BOR • Establish the safety and tolerability of AMG 420 in subjects with RRMM ; Primary end point(s): Phase 1b • Dose-limiting toxicities (DLTs), treatment-emergent adverse ev | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout study; Secondary end point(s): Phase 1b Key secondary •ORR •DOR •MRD negativity at the time of CR Secondary •DLTs, treatment-emergent adverse events, treatment-related adverse events, disease-related events, and changes in vital signs, ECGs, and clinical laboratory tests •AMG 420 PK parameters including, but not limited to, half-life (t1/2), clearance, and apparent Css • Efficacy parameters according to International Myeloma Working Group (IMWG) response criteria, per independent review committee (IRC) assessment: -Time to response -PFS -BOR •OS •TFI Phase 2 Key secondary • DOR • MRD negativity at the time of CR Secondary •Efficacy parameters according to IMWG response criteria, per IRC assessment: -Time to response -PFS -BOR •OS •TFI • Treatment-emergent adverse events, treatment-related adverse events, disease-related events, and changes in vital signs, ECGs, and clinical laboratory tests | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Romania, Spain, Switzerland, United States
Contacts
Public ContactMedinfoInternational@amgen.com
Amgen (EUROPE) GmbH
Outcome results
None listed