Multiple Myeloma
Conditions
Brief summary
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.
Interventions
DRUGOprozomib
Study subjects will receive oprozomib administered orally.
DRUGMelphalan
Study subjects will receive melphalan 9 mg/m2.
DRUGPrednisone
Study subjects will receive prednisone 60 mg/m2.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Newly diagnosed symptomatic multiple myeloma patients who are transplant ineligible with measureable disease as indicated by one or more of the following: 1. Serum M-protein ≥ 500 mg/dL 2. Urine M-protein ≥ 200 mg/24 hour 3. Serum Free Light Chain: Involved free light chain (FLC) level ≥ 10 mg/dL, provided serum FLC ratio is abnormal 2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 3. Creatinine clearance (CrCl) ≥ 30 mL/min, either measured or calculated using the formula of Cockcroft and Gault \[(140 - age) × mass (kg) / (72 × serum creatinine mg/dL)\]. Multiply result by 0.85 if female. Key
Exclusion criteria
1. Any prior systemic antimyeloma therapy except oral steroids (dexamethasone up to a total dose of 160 mg or equivalent within 14 days prior to the first dose of study treatment is allowed). Use of topical or inhaled steroids is acceptable. 2. Congestive heart failure (New York Hearth Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to first dose 3. Known or suspected HIV, active Hepatitis A, B C or virus infection (Exception: Subjects with chronic or cleared HBV and HCV infection and stable liver function tests \[bilirubin, AST\] will be allowed). 4. Significant neuropathy (Grade 2 with pain or higher) at the time of first dose. 5. Plasma cell leukemia. 6. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 7. Known amyloidosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) - Phase 2 | 39 months | CRR defined as a best overall response of sCR or CR according to the IMWG-URC. |
| Maximum Tolerated Dose (MTD) - Phase 1b | 42 weeks | 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. |
| Overall Response Rate (ORR) - Phase 2 | 39 months | ORR defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) and Serious Adverse Events (SAEs) - Phase 2 | Collected from signing of informed consent and throughout study until 30 days after the last dose of study treatment (up to 58 weeks) | Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to the NCI-CTCAE (Version 4.03). |
| Progression-free Survival (PFS) | 39 months | 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. |
| Population Pharmacokinetic (PK) parameters - apparent clearance and volume of distribution | 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 | 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. |
| Duration of Response (DOR) | 39 months | Duration of Response (DOR) is defined as the time from evidence of PR or better to disease progression or death due to any cause. |
Countries
Greece, Italy, Netherlands
Outcome results
None listed