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

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Oprozomib

Melphalan

Prednisone

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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
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.

Key Exclusion Criteria:

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

Sites / Locations

Department of Clinical Therapeutics, University of Athens
Ospedale Oncologico Regionale
Azienda Ospedaliera Universitaria S Martino
AOU Maggiore della Carita, SCDU Heamatology
University of Rome
Hospital City of Health and Science of Turin, Hematology 1 Division
Vrijc Universiteit Medisch Centrum, Department of Hematology
Erasmus MC, Department of Hematology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Oprozomib with Melphalan and Prednisone (OMP)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Overall Response Rate (ORR) - Phase 2

ORR defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC.

Complete Response Rate (CRR) - Phase 2

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

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

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)

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)

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.

Full Information

NCT ID

NCT02072863

First Posted

February 25, 2014

Last Updated

April 28, 2017

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT02072863

Brief Title

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

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

January 2014 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Oprozomib with Melphalan and Prednisone (OMP)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Oprozomib

Intervention Description

Study subjects will receive oprozomib administered orally.

Intervention Type

Drug

Intervention Name(s)

Melphalan

Intervention Description

Study subjects will receive melphalan 9 mg/m2.

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

Study subjects will receive prednisone 60 mg/m2.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) - Phase 1b

Description

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.

Time Frame

42 weeks

Title

Overall Response Rate (ORR) - Phase 2

Description

ORR defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC.

Time Frame

39 months

Title

Complete Response Rate (CRR) - Phase 2

Description

CRR defined as a best overall response of sCR or CR according to the IMWG-URC.

Time Frame

39 months

Secondary Outcome Measure Information:

Title

Adverse Events (AEs) and Serious Adverse Events (SAEs) - Phase 2

Description

Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to the NCI-CTCAE (Version 4.03).

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)

Title

Population Pharmacokinetic (PK) parameters - apparent clearance and volume of distribution

Description

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

Title

Duration of Response (DOR)

Description

Duration of Response (DOR) is defined as the time from evidence of PR or better to disease progression or death due to any cause.

Time Frame

39 months

Title

Progression-free Survival (PFS)

Description

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.

Time Frame

39 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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. Key Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Department of Clinical Therapeutics, University of Athens

City

Athens

State/Province

Attica

Country

Greece

Facility Name

Ospedale Oncologico Regionale

City

Rionero in Vulture

State/Province

Potenza

Country

Italy

Facility Name

Azienda Ospedaliera Universitaria S Martino

City

Genova

Country

Italy

Facility Name

AOU Maggiore della Carita, SCDU Heamatology

City

Novara

Country

Italy

Facility Name

University of Rome

City

Rome

Country

Italy

Facility Name

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

City

Turin

Country

Italy

Facility Name

Vrijc Universiteit Medisch Centrum, Department of Hematology

City

Amsterdam

Country

Netherlands

Facility Name

Erasmus MC, Department of Hematology

City

Rotterdam

Country

Netherlands

12. IPD Sharing Statement

Learn more about this trial

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

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