Multiple myeloma MedDRA version: 17.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Oprozomib Tablets
Product Code: ONX0912
Pharmaceutical Form: Tablet
INN or Proposed INN: Oprozomib
CAS Number: 935888-69-0
Current Sponsor code: ONX0912
Concentration unit: mg milligram(
Sponsors
Onyx Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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: a. Serum M-protein = 500 mg/dL b. Urine M-protein = 200 mg/24 hour c. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 19 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
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 HIV, Hepatitis B virus and Hepatitis C virus infection (Exception: Subjects with chronic or cleared HBV and HCV infection and stable liver function tests [bilirubin, AST] will be allowed. 4. Significant neurotoxicity (Grade 2 with pain or higher) at the time of enrollment. 5. Plasma cell leukemia 6. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 7. Known amyloidosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b: - To establish the MTD of oprozomib when administered orally in combination with melphalan and prednisone (OMP) Phase 2: - To estimate the overall response rate (ORR) and complete response rate (CRR) of the OMP combination;Secondary Objective: - To evaluate the safety and tolerability of oprozomib administered orally in combination with melphalan and prednisone - To evaluate population PK parameter estimates of oprozomib and variability in these estimates when administered in combination with melphalan and prednisone - To estimate the duration of response (DOR) - To estimate progression-free survival (PFS);Primary end point(s): Phase 1b: - Incidence, nature, and severity of AEs and SAEs of oprozomib, given in combination with melphalan and prednisone Phase 2: - Overall response, defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC - Complete response, defined as a best overall response of either sCR or CR;Timepoint(s) of evaluation of this end point: Phase 1b: - AEs and SAEs will be evaluated at every scheduled study visit Phase 2: - Overall response and complete response will be evaluated at every scheduled visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Incidence and severity of AEs and SAEs, graded according to the NCI CTCAE (Version 4.03; Phase 2 portion only), changes in laboratory parameters, ECGs, and vital signs - Population-based PK parameters including, but not limited to clearance and volume of distribution - Duration of response, defined as the time from evidence of PR or better to disease progression or death due to any cause - Duration of PFS, defined as duration from the start of treatment to disease progression or death (due to any cause), whichever comes first;Timepoint(s) of evaluation of this end point: - AEs and SAEs will be evaluated at every scheduled study visit - Laboratory parameters will be evaluated at screening, Days 1, 5, 8, 15, 22, 29, 36-42 of each cycle - ECG will be evaluated at screening, Days 1, 5, 15, 29 of each cycle - Vital signs will be evaluated 1, 2, 5, 8, 15, 22, 29, 36-42 of each cycle - PK blood draws will be performed on Day 1 of each cycle - Response and PFS will be evaluated at each scheduled visit | — |
Countries
Greece, Netherlands
Contacts
Public ContactMedical Monitor
Onyx Therapeutics, Inc.
Outcome results
None listed