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 OPZ003 was halted during dose-escalation.
Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma
Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma
2 other identifiers
interventional
22
1 country
14
Brief Summary
The primary objectives of this study included the following: Phase 1b:
- To establish the maximum tolerated dose (MTD) of oprozomib given in combination with lenalidomide and dexamethasone (ORd) or with cyclophosphamide and dexamethasone (OCyd)
- To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide Phase 2:
- To estimate the antitumor activity of each combination regimen, as measured by overall response rate (ORR) and complete response rate (CRR)
- To evaluate the safety and tolerability of each combination regimens, as assessed by the type, incidence, severity and seriousness of adverse events, and abnormalities in selected laboratory analytes
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 multiple-myeloma
Started Oct 2013
Typical duration for phase_1 multiple-myeloma
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 13, 2013
CompletedFirst Posted
Study publicly available on registry
June 20, 2013
CompletedStudy Start
First participant enrolled
October 28, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 23, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
September 23, 2019
CompletedResults Posted
Study results publicly available
March 3, 2021
CompletedNovember 14, 2022
November 1, 2022
5.9 years
June 13, 2013
February 10, 2021
November 10, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Dose-Limiting Toxicities (DLTs)
DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. A DLT is defined as any of the following treatment-related events: * Any ≥ Grade 3 nonhematologic toxicity with the following conditions: * ≥ Grade 3 nausea, vomiting, diarrhea, or constipation only if for \> 7 days despite optimal supportive care * Asymptomatic Grade 3 hypophosphatemia, Grade 3 hyperglycemia or toxicity solely due to dexamethasone, ≥ Grade 3 rash attributed to lenalidomide, and Grade 3 fatigue for \< 14 days were not considered DLTs * Grade 4 neutropenia: absolute neutrophil count (ANC) \< 0.5 × 10\^9/L lasting ≥ 7 days, despite myeloid growth factor support * Febrile neutropenia * Grade 4 thrombocytopenia for ≥ 7 days or \< 7 days with ≥ Grade 2 clinically significant bleeding or \< 10,000 platelets requiring platelet transfusion, or Grade ≥ 3 with clinically significant bleeding or requiring platelet transfusion.
Cycle 1, 28 days
Number of Participants With Treatment-emergent Adverse Events (AEs)
Adverse events (AEs) were graded using 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 are those considered related to at least 1 study drug by the investigator.
From first dose of any study treatment to 30 days after last dose; median duration of treatment was 29.1, 12.4, 11.3, 66.6, 7.8, and 46.4 weeks in each treatment group, respectively.
Secondary Outcomes (4)
Plasma Oprozomib Concentration
Cycle 1 day 1 at 1 to 2.5 hours and 2.75 to 5 hours after end of infusion (EOI) and cycle 3 day 1 at predose and 1 to 2.5 hours and 2.75 to 5 hours after EOI.
Overall Response Rate (ORR)
Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median duration of treatment at the analysis cutoff date of 18 July 2016 was 29.1, 12.4, 11.3, 66.6, 7.8 and 46.4 weeks in each group, respectively
Duration of Response (DOR)
Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median time on follow-up at the analysis cut-off date of 18 July 2016 was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively.
Progression-Free Survival (PFS)
From first dose of study drug through the data cut-off date of 18 July 2016; median time on follow-up was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively
Study Arms (6)
Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone
EXPERIMENTALParticipants 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.
Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone
EXPERIMENTALParticipants received oprozomib 180 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.
Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone
EXPERIMENTALParticipants received oprozomib 210 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.
Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone
EXPERIMENTALParticipants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.
Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone
EXPERIMENTALParticipants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.
Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone
EXPERIMENTALParticipants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Interventions
Extended release (ER) tablets administered orally
Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.
Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.
Administered orally at 300 mg/m² (up to a maximum of 600 mg) on days 1, 8, and 15 of each 28-day cycle for a maximum of 8 cycles of therapy (approximately 8 months).
Eligibility Criteria
You may qualify if:
- Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated per the National Comprehensive Cancer Network (NCCN) guidelines, and for whom a hematopoietic stem cell transplant is not planned or scheduled during the study or are considered ineligible for hematopoietic stem cell transplant, with measurable disease
- Creatinine clearance of ≥ 50 mL/min (measured or calculated using the Cockcroft and Gault formula)
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). Use of topical or inhaled steroids is acceptable
- Radiation therapy within 2 weeks prior to first dose
- Major surgery within 3 weeks prior to first dose
- Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose
- Clinical significant gastrointestinal bleeding in the 6 months prior to Cycle 1 Day 1 (C1D1) first dose
- Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of first dose
- Other malignancy within the past 3 years except those considered cured by surgical resection including some cases of: with the exception of adequately treated basal or squamous cell carcinoma of the skin, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the breast or cervix, carcinoma in situ of the breast, prostate cancer with Gleason Score 6 or less with stable prostate specific antigen levels, or cancer considered cured by surgical resection
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (14)
Clearview Cancer Institute
Huntsville, Alabama, United States
Providence St. Joseph's Hospital
Burbank, California, United States
David Geffen School of Medicine at UCLA
Los Angeles, California, United States
Monterey Bay Oncology Corp DBA Pacific Cancer Care
Salinas, California, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
H. Lee Moffit Cancer Center & Research Institute
Tampa, Florida, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Center for Cancer & Blood Disorders
Bethesda, Maryland, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Cleveland Clinic
Cleveland, Ohio, United States
University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Amgen Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 13, 2013
First Posted
June 20, 2013
Study Start
October 28, 2013
Primary Completion
September 23, 2019
Study Completion
September 23, 2019
Last Updated
November 14, 2022
Results First Posted
March 3, 2021
Record last verified: 2022-11