The purpose of Phase 1b of the study is to determine the maximum tolerated dose (MTD) of oprozomib in combination with melphalan and prednisone (OMP). The purpose of Phase 2 of the study is to estimate the overall response rate (ORR) and complete response rate (CRR) of the OMP combination.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Study subjects will receive oprozomib administered orally.
Study subjects will receive melphalan 9 mg/m2.
Study subjects will receive prednisone 60 mg/m2.
Department of Clinical Therapeutics, University of Athens
Athens, Attica, Greece
Ospedale Oncologico Regionale
Rionero in Vulture, Potenza, Italy
Azienda Ospedaliera Universitaria S Martino
Genova, Italy
AOU Maggiore della Carita, SCDU Heamatology
Novara, Italy
Maximum Tolerated Dose (MTD) - Phase 1b
MTD is defined as the highest dose at which a DLT is observed in less than 2 of 6 evaluable subjects occurring within the 4 weeks after the first dose of combination therapy.
Time frame: 42 weeks
Overall Response Rate (ORR) - Phase 2
ORR defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC.
Time frame: 39 months
Complete Response Rate (CRR) - Phase 2
CRR defined as a best overall response of sCR or CR according to the IMWG-URC.
Time frame: 39 months
Adverse Events (AEs) and Serious Adverse Events (SAEs) - Phase 2
Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to the NCI-CTCAE (Version 4.03).
Time frame: Collected from signing of informed consent and throughout study until 30 days after the last dose of study treatment (up to 58 weeks)
Population Pharmacokinetic (PK) parameters - apparent clearance and volume of distribution
Evaluate population pharmacokinetic (PK) parameter estimates of oprozomib and variability in these estimates when administered in combination with melphalan and prednisone using a sparse sampling strategy and population-based analysis methodology.
Time frame: 2 postdose time points in Cycle 1 Day 1, 1 predose and 2 postdose time points on Cycle 3 Day 1 and Cycle 5 Day 1
Duration of Response (DOR)
Duration of Response (DOR) is defined as the time from evidence of PR or better to disease progression or death due to any cause.
Time frame: 39 months
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University of Rome
Rome, Italy
Hospital City of Health and Science of Turin, Hematology 1 Division
Turin, Italy
Vrijc Universiteit Medisch Centrum, Department of Hematology
Amsterdam, Netherlands
Erasmus MC, Department of Hematology
Rotterdam, Netherlands
Progression-free Survival (PFS)
Progression-free survival is defined as the time from the first day of study treatment (Cycle 1 Day 1) to the earlier of disease progression or death due to any cause.
Time frame: 39 months