A Study of Oprozomib, Melphalan, and Prednisone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Phase 1b/2, Multicenter, Open-label Study of Oprozomib, Melphalan, and Prednisone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02072863
• Other study ID #: OPZ006
• Secondary ID: 2013-002125-27
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 25, 2014
• Last updated: April 28, 2017
• Start date: January 2014
• Est. completion date: September 2015

Study information

• Verified date: April 2017
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: September 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Oprozomib
Study subjects will receive oprozomib administered orally.
• Melphalan
Study subjects will receive melphalan 9 mg/m2.
• Prednisone
Study subjects will receive prednisone 60 mg/m2.

Locations

Country	Name	City	State
Greece	Department of Clinical Therapeutics, University of Athens	Athens	Attica
Italy	Azienda Ospedaliera Universitaria S Martino	Genova
Italy	AOU Maggiore della Carita, SCDU Heamatology	Novara
Italy	Ospedale Oncologico Regionale	Rionero in Vulture	Potenza
Italy	University of Rome	Rome
Italy	Hospital City of Health and Science of Turin, Hematology 1 Division	Turin
Netherlands	Vrijc Universiteit Medisch Centrum, Department of Hematology	Amsterdam
Netherlands	Erasmus MC, Department of Hematology	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

Greece,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	42 weeks
Primary	Overall Response Rate (ORR) - Phase 2	ORR defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC.	39 months
Primary	Complete Response Rate (CRR) - Phase 2	CRR defined as a best overall response of sCR or CR according to the IMWG-URC.	39 months
Secondary	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).	Collected from signing of informed consent and throughout study until 30 days after the last dose of study treatment (up to 58 weeks)
Secondary	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.	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
Secondary	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.	39 months
Secondary	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.	39 months