Clinical trial NCT02072863: A Study of Oprozomib, Melphalan, and Prednisone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma
Official title: Phase 1b/2, Multicenter, Open-label Study of Oprozomib, Melphalan, and Prednisone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-02-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) - Phase 1b
timeFrame: 42 weeks
measure: Overall Response Rate (ORR) - Phase 2
timeFrame: 39 months
measure: Complete Response Rate (CRR) - Phase 2
timeFrame: 39 months
Secondary outcomes:
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs) - Phase 2
timeFrame: Collected from signing of informed consent and throughout study until 30 days after the last dose of study treatment (up to 58 weeks)
measure: Population Pharmacokinetic (PK) parameters - apparent clearance and volume of distribution
timeFrame: 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
measure: Duration of Response (DOR)
timeFrame: 39 months
measure: Progression-free Survival (PFS)
timeFrame: 39 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Department of Clinical Therapeutics, University of Athens
state: Attica
city: Rionero in Vulture
country: Italy
facility: Ospedale Oncologico Regionale
state: Potenza
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria S Martino
city: Novara
country: Italy
facility: AOU Maggiore della Carita, SCDU Heamatology
city: Rome
country: Italy
facility: University of Rome
city: Turin
country: Italy
facility: Hospital City of Health and Science of Turin, Hematology 1 Division
city: Amsterdam
country: Netherlands
facility: Vrijc Universiteit Medisch Centrum, Department of Hematology
city: Rotterdam
country: Netherlands
facility: Erasmus MC, Department of Hematology
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: