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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02072863
First Posted: February 27, 2014
Last Update Posted: May 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Amgen
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma Drug: Oprozomib Drug: Melphalan Drug: Prednisone Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b/2, Multicenter, Open-label Study of Oprozomib, Melphalan, and Prednisone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) - Phase 1b [ Time Frame: 42 weeks ]
    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.

  • Overall Response Rate (ORR) - Phase 2 [ Time Frame: 39 months ]
    ORR defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC.

  • Complete Response Rate (CRR) - Phase 2 [ Time Frame: 39 months ]
    CRR defined as a best overall response of sCR or CR according to the IMWG-URC.


Secondary Outcome Measures:
  • Adverse Events (AEs) and Serious Adverse Events (SAEs) - Phase 2 [ Time Frame: Collected from signing of informed consent and throughout study until 30 days after the last dose of study treatment (up to 58 weeks) ]
    Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to the NCI-CTCAE (Version 4.03).

  • Population Pharmacokinetic (PK) parameters - apparent clearance and volume of distribution [ Time Frame: 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 ]
    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.

  • Duration of Response (DOR) [ Time Frame: 39 months ]
    Duration of Response (DOR) is defined as the time from evidence of PR or better to disease progression or death due to any cause.

  • Progression-free Survival (PFS) [ Time Frame: 39 months ]
    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.


Enrollment: 9
Study Start Date: January 2014
Study Completion Date: September 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02072863


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

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02072863     History of Changes
Other Study ID Numbers: OPZ006
2013-002125-27 ( EudraCT Number )
First Submitted: February 25, 2014
First Posted: February 27, 2014
Last Update Posted: May 2, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Melphalan
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors