Relapsed and Refractory Multiple MyelomaPhase 3NCT03029234
Carfilzomib in Combination With Dexamethasone (Kd) in Chinese Patients With Relapsed & Refractory Multiple Myeloma
A Phase 3 study testing Dexamethasone and Carfilzomib in people with Relapsed and Refractory Multiple Myeloma, run by Amgen at 17 sites in China.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and overall response rate of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in China. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed and Refractory Multiple Myeloma
- What is being tested?
- Dexamethasone and Carfilzomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 17 sitesChina
- Study dates
- 31 Mar 2017to 4 Jun 2021
- Phase
- Phase 3
- 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
Inclusion Criteria: - Multiple myeloma - Subjects must have measurable disease, defined as one or more of the following: -- Serum M-protein ≥ 1 g/dL -- Urine M-protein ≥ 200 mg/24 hours -- In subjects without measurable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal κ/λ ratio - Subjects must have been responsive (ie, achieved a minimal response [MR] or better) to at least one of their prior treatment regimens - Refractory to the most recently received therapy. Refractory disease defined as ≤ 25% response to, or progressing during therapy or within 60 days after completion of therapy - Subjects must have received ≥ 2 prior regimens. Induction therapy and stem cell transplant (± maintenance) will be considered as 1 regimen - Subjects must have received prior treatment with bortezomib and an immunomodulatory drug - Subjects must have received an alkylating agent or anthracycline alone or in combination with other myeloma treatments (this may include high dose melphalan as part of the conditioning regimen prior to a stem cell transplant) - Males and females ≥ 18 years of age - Life expectancy of more than 3 months - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 - Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 times the ULN - Absolute neutrophil count (ANC) ≥ 1,000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³ • Subjects should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count • Screening ANC should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) support for ≥ 1 week and pegylated G-CSF for ≥ 2 weeks • Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin - Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min. Calculated CrCl should be performed by using a widely accepted equation (eg, the Cockcroft and Gault equation): ([140 - Age] × Mass [kg] / [72 × Creatinine mg/dL]). Multiply the result by 0.85 if the subject is female. - Left ventricular ejection fraction (LVEF) ≥ 40%; 2-dimensional transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multiple gated acquisition scan (MUGA) is acceptable if ECHO is not available - Written informed consent in accordance with federal, local, and institutional guidelines - Female subjects of child-bearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use an effective method of contraception during and for 30 days following last dose of carfilzomib. This protocol defines a FCBP as a sexually mature woman who: 1) has not undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) - Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose of carfilzomib if sexually active with a FCBP. Male subjects must not donate sperm during treatment and for an additional 90 days after last dose of carfilzomib. Male subjects with pregnant partners must practice sexual abstinence or use a condom during vaginal sex. Exclusion Criteria: - Waldenström's macroglobulinemia or immunoglobulin M (IgM) multiple myeloma - Subjects who failed to achieve at least a confirmed MR on any of their prior regimens - Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum and < 200 mg/24 hour M-protein in urine and SFLC ≤ 100 mg/L (involved light chain) - Glucocorticoid therapy (prednisone > 10 mg/day or equivalent) within 3 weeks prior to Cycle 1 Day 1 - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) - Plasma cell leukemia (> 2.0 × 10⁹/L circulating plasma cells by standard differential) - Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the 3 weeks prior to Cycle 1 Day 1 - Radiation therapy or immunotherapy in the 4 weeks prior to Cycle 1 Day 1; localized radiation therapy within 1 week prior to Cycle 1 Day 1 - Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (T½) prior to Cycle 1 Day 1, whichever time is greater - Prior treatment with carfilzomib - Major surgery within 3 weeks before Cycle 1 Day 1 - Congestive heart failure (CHF; New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months - Uncontrolled hypertension (a sustained systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg) - Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to Cycle 1 Day 1 - Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed) - Non-hematologic malignancy within the past 3 years except: -- Adequately treated basal cell or squamous cell skin cancer, -- Carcinoma in situ of the cervix, or -- Prostate cancer < Gleason Score 6 with stable prostate-specific antigen - Subjects with treatment-related myelodysplastic syndrome - Significant neuropathy (Grade 3, 4, or Grade 2 with pain) at the time of baseline evaluation - Subjects in whom the required program of fluid hydration is contraindicated, eg, due to pre-existing pulmonary, cardiac, or renal impairment - Subjects with known or suspected amyloidosis - Subjects with pleural effusions requiring thoracentesis - Subjects with ascites requiring paracentesis - Any clinically significant medical disease or condition, that in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent - Female subjects who are pregnant or lactating, or planning to become pregnant during treatment and for an additional 30 days after discontinuing carfilzomib. - Serious psychiatric or medical conditions that could interfere with treatment
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
China17 sites
Beijing Chao Yang Hospital, Capital Medical University
Beijing, Beijing Municipality, 100020
Peking University Third Hospital
Beijing, Beijing Municipality, 100191
Peking Union Medical College Hospital
Beijing, 100730
The First Hospital of Jilin University
Changchun, Jilin, 130021
West China Hospital, Sichuang University
Chengdu, Sichuan, 610041
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510060
Guangzhou First Peoples Hospital
Guangzhou, Guangdong, 510180
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310003
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, 200032
Shanghai Changzheng Hospital
Shanghai, 200003
The First Hospital of China Medical University
Shenyang, Liaoning, 110001
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215004
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
The Central Hospital of Wuhan
Wuhan, Hubei, 430014
Henan Cancer Hospital
Zhengzhou, Henan, 450008
About this study
Official title: An Open-label, Single-arm, Phase 3 Study of Carfilzomib in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma in China
The purpose of this study is to evaluate the safety, tolerability and overall response rate of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in China.
- Conditions
- Relapsed and Refractory Multiple Myeloma
- Being tested
- Dexamethasone, Carfilzomib
- Medical subject headings
- Recurrence, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles.
CarfilzomibDrug
Also called Kyprolis
Infusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib with Dexamethasone | Experimental | Participants will receive carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter).
Participants will also receive 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle.
Participants will receive treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, non-compliance, or intercurrent illness or worsening of a chronic condition, whichever occurs first. Receives: Drug: Dexamethasone; Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee
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.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). 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.
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).
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.
Measured: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.
Secondary outcomes (21)
Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator
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.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). 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.
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).
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.
Measured: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.
Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee
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.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). 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.
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).
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.
Measured: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.
Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator
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.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). 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.
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).
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.
Measured: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.
Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee
Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas is also required
Measured: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 8.9 months.
Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator
Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.
Measured: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.
Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee
Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.
Measured: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.
Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator
Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.
Measured: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.
Duration of Overall Response (DOR)
Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria.
PD:
- Increase of 25% from lowest response value in any of the following:
- Serum M-component (absolute increase ≥ 0.5 g/dL) and/or
- Urine M-component (absolute increase ≥ 200 mg/24 hours)
- In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL)
- Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas
- Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.
DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment.
DOR was determined based on both investigator and independent review committee response assessments.
Measured: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Duration of Clinical Benefit (DCB)
Duration of clinical benefit (DCB) is defined as the time from first evidence of MR or better to disease progression or death due to any cause based on the (IMWG-URC criteria. DCB was estimated using the Kaplan-Meier method; participants with no disease progression or death at the analysis cut-off date were censored at their last disease assessment date.
Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.
Measured: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the time from first dose of any study treatment to the earlier of disease progression or death due to any cause according to the IMWG-URC criteria. PFS was analyzed using the Kaplan-Meier method; participants with no disease progression or death at the time of the data cut-off date were censored at the date of their last disease assessment; participants who started new anti-cancer therapy before disease progression or death were censored at their last disease assessment prior to starting new anti-cancer therapy.
Progression-free survival was determined based on both investigator and independent review committee response assessments.
Measured: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Overall Survival (OS)
Overall survival (OS) is defined as the time from the first dose of any study treatment to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at their date of last contact (last known to be alive).
Measured: From first dose until the data cut-off date of 15 March 2019; median time on follow-up for survival was 15.3 months.
Time to Response (TTR)
Time to response (TTR) is the time from the first dose of any study treatment to the first confirmed response (PR or better) based on both investigator and independent review committee response assessments.
Measured: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib
Cmax is the maximum observed plasma concentration over the concentration-time profile of carfilzomib.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Time to Maximum Plasma Concentration (Tmax) of Carfilzomib
Tmax of carfilzomib is the time at which maximum observed plasma concentrations of carfilzomib were observed.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib
AUClast of carfilzomib is the total area under the concentration-time curve beginning from time 0 to the time of the last measurable concentration of carfilzomib.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib
AUC0-inf of carfilzomib is the total area under the concentration-time curve beginning from time 0 extrapolated to infinity following carfilzomib dosing.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Terminal Elimination Half-Life (T½) for Carfilzomib
The terminal elimination half-life is the time required for plasma concentrations to fall by 50% in the terminal phase of the concentration-time profile.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion
Systemic clearance is a measure of the ability of the body to eliminate drug, expressed in units of volume per time.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Volume of Distribution (Varea) of Carfilzomib
Volume of distribution is a pharmacokinetic parameter relating the amount of drug in the body to the concentration of drug in plasma.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Volume of Distribution at Steady State (Vss) for Carfilzomib
Volume of distribution at steady-state is a pharmacokinetic parameter that relates the amount of drug in the body at steady-state to the concentration of drug in the plasma.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib
MRTlast is the mean residence time observed from time 0 until the time of the last quantifiable concentration.
Measured: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start31 Mar 2017
- Primary completion5 Nov 2018
- Study completion4 Jun 2021
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed and Refractory 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Onyx Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029234
- Sponsor's protocol ID
- 20140242
- Other IDs
- CFZ005
- Status last verified
- Apr 2022
- First submitted
- 11 Nov 2016
- Last updated
- 25 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
Du J, Fang B, Li J, Jin J, Wang S, Zou D, Cai Z, Wang H, Hu J, Li W, Fu C, Shao Z, Xia Z, Liu P, Niu T, Tang ET, Kimball AS, Hou J, Chen W. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol. 2021 Mar;113(3):422-429. doi: 10.1007/s12185-020-03044-z. Epub 2021 Jan 3.
PubMed 33389656
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm, Phase 3 Study of Carfilzomib in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma in China
- ClinicalTrials.gov ID
- NCT03029234
- Acronym / sponsor ID
- 20140242
- Conditions
- Relapsed and Refractory Multiple Myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Onyx Therapeutics, Inc.
- Study start
- 31 Mar 2017 (actual)
- Primary completion
- 5 Nov 2018 (actual)
- Study completion
- 4 Jun 2021 (actual)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Posted 21 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability and overall response rate of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in China.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib with Dexamethasone | Experimental | Drug: Dexamethasone, Drug: CarfilzomibParticipants will receive carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants will also receive 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle. Participants will receive treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, non-compliance, or intercurrent illness or worsening of a chronic condition, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Dexamethasone20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles. | Drug | Carfilzomib with Dexamethasone |
| CarfilzomibAlso: KyprolisInfusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle. | Drug | Carfilzomib with Dexamethasone |
Primary outcome
Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee
Time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.
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. sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). 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. 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). 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.
21 secondary outcomes
Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator
Time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.
Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee
Time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.
Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator
Time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.
Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee
Time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 8.9 months.
Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator
Time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.
Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee
Time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.
Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator
Time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.
Duration of Overall Response (DOR)
Time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Duration of Clinical Benefit (DCB)
Time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Progression-free Survival (PFS)
Time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Overall Survival (OS)
Time frame: From first dose until the data cut-off date of 15 March 2019; median time on follow-up for survival was 15.3 months.
Time to Response (TTR)
Time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Time to Maximum Plasma Concentration (Tmax) of Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Terminal Elimination Half-Life (T½) for Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Volume of Distribution (Varea) of Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Volume of Distribution at Steady State (Vss) for Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib
Time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33389656Du J, Fang B, Li J, Jin J, Wang S, Zou D, Cai Z, Wang H, Hu J, Li W, Fu C, Shao Z, Xia Z, Liu P, Niu T, Tang ET, Kimball AS, Hou J, Chen W. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol. 2021 Mar;113(3):422-429. doi: 10.1007/s12185-020-03044-z. Epub 2021 Jan 3.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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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
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexamethasone and Carfilzomib in people with Relapsed and Refractory Multiple Myeloma, run by Amgen at 17 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 25 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in China. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 21 Nov 2019). 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?
Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee (time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03029234, which also lists 1 linked publication.
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 25 May 2022.