Multiple MyelomaPhase 1/2NCT01881789
Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma
A Phase 1/2 study testing Oprozomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Amgen at 14 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Oprozomib, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 14 sitesUnited States
- Study dates
- 28 Oct 2013to 23 Sep 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Center for Cancer & Blood Disorders
Bethesda, Maryland
Providence St. Joseph's Hospital
Burbank, California
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
University of Chicago Medical Center
Chicago, Illinois
Cleveland Clinic
Cleveland, Ohio
Colorado Blood Cancer Institute
Denver, Colorado
University of Texas M.D. Anderson Cancer Center
Houston, Texas
Clearview Cancer Institute
Huntsville, Alabama
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana
David Geffen School of Medicine at UCLA
Los Angeles, California
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin
Monterey Bay Oncology Corp DBA Pacific Cancer Care
Salinas, California
Fred Hutchinson Cancer Research Center
Seattle, Washington
H. Lee Moffit Cancer Center & Research Institute
Tampa, Florida
About this study
Official title: 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
The primary objectives of this study included the following:
Phase 1b:
Read more
- 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
Read the detailed description
Phase 1b used a standard 3 + 3 dose-escalation scheme to determine the MTD. For each combination regimen, oprozomib doses were to be escalated in sequential cohorts of 3 participants with expansion to up to 6 participants if a dose-limiting toxicity (DLT) was observed in 1 of the first 3 participants. The doses of lenalidomide, cyclophosphamide, and dexamethasone were to remain fixed in all dose cohorts.
The phase 2 portion of the study was to include up to 35 additional participants in each of the 2 combination regimens, treated at the recommended phase 2 dose (RP2D) of oprozomib that was identified during the phase 1b portion of the study in order to better characterize safety and tolerability, and antimyeloma activity.
This study was stopped by sponsor decision during the dose escalation in phase 1b prior to initiation of phase 2.
- Conditions
- Multiple Myeloma
- Being tested
- Oprozomib, Lenalidomide, Dexamethasone, Cyclophosphamide
- Keywords
- multiple myeloma, proteasome inhibitor, oprozomib, orpozomib tablets
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OprozomibDrug
Also called Oprozomib ER tablets
Extended release (ER) tablets administered orally
LenalidomideDrug
Also called Revlimid
Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.
DexamethasoneDrug
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.
CyclophosphamideDrug
Also called Cytoxan
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).
| Study group | Role | What they receive |
|---|---|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + 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 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. Receives: Drug: Oprozomib; Drug: Lenalidomide; Drug: Dexamethasone |
| Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Experimental | Participants 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. Receives: Drug: Oprozomib; Drug: Lenalidomide; Drug: Dexamethasone |
| Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Experimental | Participants 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. Receives: Drug: Oprozomib; Drug: Lenalidomide; Drug: Dexamethasone |
| Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Experimental | Participants 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. Receives: Drug: Oprozomib; Drug: Lenalidomide; Drug: Dexamethasone |
| Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Experimental | Participants 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. Receives: Drug: Oprozomib; Drug: Lenalidomide; Drug: Dexamethasone |
| Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | Experimental | Participants 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. Receives: Drug: Oprozomib; Drug: Dexamethasone; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Plasma samples for oprozomib concentration assays were only collected for participants in the 5/14 dosing schedule groups.
Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.
Measured: 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)
ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).
CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM).
Measured: 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)
Duration of response was defined as the time from first evidence of partial response (PR) or better to confirmation of disease progression or death due to any cause.
Median DOR was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment.
Measured: 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)
Progression-free survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever occurred first. Median PFS was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2013 (estimated)
- Study start28 Oct 2013
- Primary completion23 Sep 2019
- Study completion23 Sep 2019
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01881789
- Sponsor's protocol ID
- OPZ003
- Other IDs
- 20130410
- Status last verified
- Nov 2022
- First submitted
- 13 Jun 2013
- Last updated
- 14 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01881789
- Acronym / sponsor ID
- OPZ003
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, proteasome inhibitor, oprozomib, orpozomib tablets
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 28 Oct 2013 (actual)
- Primary completion
- 23 Sep 2019 (actual)
- Study completion
- 23 Sep 2019 (actual)
- First posted
- 20 Jun 2013 (estimated)
- Results
- Posted 3 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Phase 1b used a standard 3 + 3 dose-escalation scheme to determine the MTD. For each combination regimen, oprozomib doses were to be escalated in sequential cohorts of 3 participants with expansion to up to 6 participants if a dose-limiting toxicity (DLT) was observed in 1 of the first 3 participants. The doses of lenalidomide, cyclophosphamide, and dexamethasone were to remain fixed in all dose cohorts.
The phase 2 portion of the study was to include up to 35 additional participants in each of the 2 combination regimens, treated at the recommended phase 2 dose (RP2D) of oprozomib that was identified during the phase 1b portion of the study in order to better characterize safety and tolerability, and antimyeloma activity.
This study was stopped by sponsor decision during the dose escalation in phase 1b prior to initiation of phase 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Experimental | Drug: Oprozomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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 | Experimental | Drug: Oprozomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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 | Experimental | Drug: Oprozomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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 | Experimental | Drug: Oprozomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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 | Experimental | Drug: Oprozomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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 | Experimental | Drug: Oprozomib, Drug: Dexamethasone, Drug: CyclophosphamideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OprozomibAlso: Oprozomib ER tabletsExtended release (ER) tablets administered orally | Drug | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone, Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone, Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone |
| LenalidomideAlso: RevlimidAdministered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles. | Drug | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone, Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone |
| DexamethasoneAdministered 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. | Drug | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone, Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone, Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone, Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone |
| CyclophosphamideAlso: CytoxanAdministered 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). | Drug | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone |
Primary outcome
Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1, 28 days
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.
Number of Participants With Treatment-emergent Adverse Events (AEs)
Time frame: 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.
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.
4 secondary outcomes
Plasma Oprozomib Concentration
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oprozomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Amgen at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1, 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2022.