NCT01999335|TerminatedPhase 1ResultsDMC

Study Stopped

A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in OPZ007 was halted during dose-expansion.

A Study of Oprozomib, Pomalidomide, and Dexamethasone in Adults With Primary Refractory or Relapsed and Refractory Multiple Myeloma

Phase 1b/3 Multicenter Study of Oprozomib, Pomalidomide, and Dexamethasone in Primary Refractory or Relapsed and Refractory Multiple Myeloma Subjects

Amgen ClinicalTrials.gov

Compare

2 other identifiers

OPZ00720130411

Study Type

interventional

Target

Locations

1 country

Sites

Timeline

RegisteredDec 2013

StartedJul 2014

CompletionApr 2019

Brief Summary

The purpose of the Phase 1 part of the study is to determine the maximum tolerated dose and assess the safety, tolerability and activity of oprozomib in combination with pomalidomide and dexamethasone in adults with primary refractory or relapsed and refractory multiple myeloma. The purpose of the Phase 3 part of the study is to compare the efficacy for adults with primary refractory or relapsed and refractory multiple myeloma who are randomized to either oprozomib or placebo in combination with pomalidomide and dexamethasone.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_1 multiple-myeloma

Timeline

Completed

Started Jul 2014

Typical duration for phase_1 multiple-myeloma

Geographic Reach

1 country

17 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

4.7 years study duration

First Submitted

Initial submission to the registry

November 25, 2013

Completed

8 days until next milestone

First Posted

Study publicly available on registry

December 3, 2013

Completed

8 months until next milestone

Study Start

First participant enrolled

July 30, 2014

Completed

4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 25, 2019

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 25, 2019

Completed

2 years until next milestone

Results Posted

Study results publicly available

April 27, 2021

Completed

Last Updated

April 27, 2021

Status Verified

March 1, 2021

Enrollment Period

4.7 years

First QC Date

November 25, 2013

Results QC Date

February 23, 2021

Last Update Submit

March 31, 2021

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, defined as any of the following treatment-related events occurring within 4 weeks after the first dose of therapy: Any grade ≥ 3 nonhematologic toxicity, except: Grade 3 asymptomatic electrolyte abnormalities or hypophosphatemia for \< 24 hours; Grade 3 nausea, vomiting or diarrhea unless for \> 3 days despite optimal supportive care; Grade 3 fatigue for \< 14 days; Grade ≥ 3 hyperglycemia or toxicity attributed to dexamethasone and Grade ≥ 3 rash attributed to pomalidomide. Hematologic toxicities: * Grade 4 neutropenia: Absolute neutrophil count \< 0.5 × 10\^9/L for ≥ 7 days despite adequate growth factor support; febrile neutropenia * Thrombocytopenia: Grade 4 for ≥ 7 days, or Grade 4 for \< 7 days with grade 2 clinically significant bleeding or \< 10,000 platelets requiring transfusion, or Grade 3 with clinically significant bleeding or requiring platelet transfusion.
Cycle 1, 28 days
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Adverse events (AEs) were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. A serious AE is an event that met 1 or more of the following criteria: * Death * Life-threatening experience * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly birth defect in the offspring of an exposed female subject or offspring of a female partner of a male subject * Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent an outcome listed above. Treatment-related AEs (TRAE) are those considered related to at least 1 study drug by the investigator.
From first dose of any study drug up to 30 days after the last dose; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
Number of Participants With Post-Baseline Grade 3 or 4 Laboratory Toxicities
Laboratory abnormalities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Full chemistry panel included sodium, potassium, calcium, alkaline phosphatase, blood urea nitrogen, uric acid, lactate dehydrogenase, creatinine, chloride, bicarbonate, glucose, total protein, albumin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), phosphorous, and magnesium. Complete blood count (CBC) with differential included hemoglobin, hematocrit, white blood cell (WBC) count with complete manual or automated differential (total neutrophils, lymphocytes, monocytes, eosinophils, basophils; reported as absolute counts), red blood cell (RBC) count, and platelet count.
Cycles 1 and 2 days 1, 5, 15, and 19 and days 3 and 8 of cycle 1, and day 1 of each cycle from cycle 3 thereafter until the end of treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.

Secondary Outcomes (6)

Overall Response Rate (ORR)
Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
Clinical Benefit Rate (CBR)
Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
Maximum Plasma Concentration (Cmax) of Oprozomib
Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
Time to Maximum Plasma Concentration (Tmax) of Oprozomib
Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of Oprozomib
Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
+1 more secondary outcomes

Study Arms (5)

Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone

EXPERIMENTAL

Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.