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

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

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 Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Oprozomib; Drug: Melphalan; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oprozomib with Melphalan and Prednisone (OMP); Subjects will receive oprozomib administered orally. The combination of oprozomib, melphalan, and prednisone (OMP) will be administered until progression of disease, unacceptable toxicity, discontinuation of study treatment for reasons other than progression or toxicity, or a maximum of 9 cycles (54 weeks), whichever occurs first.	Drug: Oprozomib; Study subjects will receive oprozomib administered orally.; Drug: Melphalan; Study subjects will receive melphalan 9 mg/m2.; Drug: Prednisone; Study subjects will receive prednisone 60 mg/m2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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

Collaborators and Investigators

• Sponsor: Amgen

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: February 25, 2014
• First Submitted That Met QC Criteria: February 25, 2014
• First Posted (Estimate): February 27, 2014

Study Record Updates

• Last Update Posted (Actual): May 2, 2017
• Last Update Submitted That Met QC Criteria: April 28, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Prednisone; Melphalan
• Other Study ID Numbers: OPZ006; 2013-002125-27 (EudraCT Number)