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

NCT02072863 | Completed Phase 1 DMC

• 2 other identifiers: OPZ0062013-002125-27
• Study Type: interventional
• Target: 9
• Locations: 3 countries
• Sites: 8

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• 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)

• 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

• Duration of Response (DOR)

  39 months

• Progression-free Survival (PFS)

  39 months

Study Arms (1)

Oprozomib with Melphalan and Prednisone (OMP)

EXPERIMENTAL

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; Drug: Melphalan; Drug: Prednisone

Interventions

Oprozomib DRUG

Study subjects will receive oprozomib administered orally.

Oprozomib with Melphalan and Prednisone (OMP)

Melphalan DRUG

Study subjects will receive melphalan 9 mg/m2.

Oprozomib with Melphalan and Prednisone (OMP)

Prednisone DRUG

Study subjects will receive prednisone 60 mg/m2.

Oprozomib with Melphalan and Prednisone (OMP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed symptomatic multiple myeloma patients who are transplant ineligible with measureable disease as indicated by one or more of the following:
• Serum M-protein ≥ 500 mg/dL
• Urine M-protein ≥ 200 mg/24 hour
• Serum Free Light Chain: Involved free light chain (FLC) level ≥ 10 mg/dL, provided serum FLC ratio is abnormal
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• 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.

You may not qualify if:

• 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.
• 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
• 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).
• Significant neuropathy (Grade 2 with pain or higher) at the time of first dose.
• Plasma cell leukemia.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Known amyloidosis

Sponsors & Collaborators

• Amgen: lead

Study Sites (8)

Department of Clinical Therapeutics, University of Athens

Athens, Attica, Greece

Location

Ospedale Oncologico Regionale

Rionero in Vulture, Potenza, Italy

Location

Azienda Ospedaliera Universitaria S Martino

Genova, Italy

Location

AOU Maggiore della Carita, SCDU Heamatology

Novara, Italy

Location

University of Rome

Rome, Italy

Location

Hospital City of Health and Science of Turin, Hematology 1 Division

Turin, Italy

Location

Vrijc Universiteit Medisch Centrum, Department of Hematology

Amsterdam, Netherlands

Location

Erasmus MC, Department of Hematology

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ONX 0912; Melphalan; Prednisone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2014
• First Posted: February 27, 2014
• Study Start: January 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: September 1, 2015
• Last Updated: May 2, 2017

Record last verified: 2017-04

Locations

NL (2); IT (5); GR (1)