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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001169-34 | EudraCT Number |
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A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with Pomalidomide and Dexamethasone
An Open-label, Phase 2 Study Treating Subjects with First or Second Relapse of Multiple Myeloma with Carfilzomib, Pomalidomide, and Dexamethasone (KPd)
This trial is designed to estimate the efficacy of a carfilzomib-based triplet in first or second relapse of multiple myeloma for subjects refractory to lenalidomide. The study is an open-label, phase 2 trial. Subjects may receive treatment until progression.
Myeloma disease status will be monitored locally for response and progression per International Myeloma Working Group (IMWG) criteria (Kumar et al, 2016) every 28 ± 7 days from cycle 1 day 1 until confirmed progressive disease (PD), death, lost to follow-up, or withdrawal of full consent (whichever occurs first), regardless of cycle duration, dose delays or treatment discontinuation. Subjects with a suspected complete response (CR) or better will have a bone marrow for minimal residual disease (MRD) assessment at 12 and 24 months (± 4 weeks) from start of treatment (unless a MRD assessment was performed within 4 months before planned assessment).
Subjects who end study drug(s) without confirmed PD are required to complete disease response assessments and report new anti-myeloma treatment every 28 ± 7 days until first subsequent anti-myeloma treatment, death, lost to follow-up, withdrawal of full consent, confirmed PD, or end of study, whichever occurs first. Subjects who discontinue treatment and either start new anti-myeloma treatment or have PD will enter long-term follow-up every 12 weeks until death or end of study.
Approximately one-third of subjects enrolled in the study will be in first relapse and two-thirds in second relapse.
This study will enroll adults ≥ 18 years of age with first or second relapse multiple myeloma.
Eligible subjects will have relapsed multiple myeloma after receiving 1 or 2 prior lines of therapy.
Subjects must be refractory to lenalidomide. Subjects may not have received prior pomalidomide. Prior exposure to a proteasome inhibitor is allowed. Subjects previously exposed to carfilzomib must have responded with at least a partial response to carfilzomib, must not have discontinued carfilzomib due to toxicity, may not have relapsed while receiving or within 60 days of the last dose of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval since their last dose of carfilzomib.
Subjects must have measurable disease per IMWG consensus criteria, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2, and at least partial response to 1 line of therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Carfilzomib combined with pomalidomide and dexamethasone | Experimental | Carfilzomib, pomalidomide, and dexamethasone (KPd) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carfilzomib | Drug | Carfilzomib will be administered intravenously over 30 ± 5 minutes, on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression. A dose of 20 mg/m^2 will be administered on day 1 of cycle 1. All subsequent doses will be 56 mg/m^2. The frequency of carfilzomib administration will be reduced to day 1 and 15 per cycle starting with cycle 13 and continued until progression or end of study. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC) | Overall response was defined as the best overall confirmed response of: Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to < 200 mg/24-h. Assessment was by IRC per International Myeloma Working Group Uniform Response Criteria (IMWG-URC). The 90% confidence intervals were estimated using the Clopper-Pearson method (1994). | From day 1 cycle 1 until the primary analysis (PA) data cutoff (DCO); the mean duration of KPd treatment as of the DCO was 42.0 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC | The MRD[-]CR rate was defined as the percentage of participants who reached MRD[-]CR at the 12 month landmark (8- to 13-month window). MRD[-]CR was defined as the achievement of CR (including sCR or better) per IMWG-URC by IRC assessment and MRD[-] status at a sensitivity of 10^-5 using next-generation sequencing based method in the bone marrow. The 90% CIs were estimated using the Clopper-Pearson method (1994). |
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Inclusion Criteria
Subject has provided informed consent prior to initiation of any study specific activities or procedures.
Male or female subjects age ≥ 18 years
First or second relapse of multiple myeloma by IMWG criteria (subjects refractory to the most recent line of therapy, excluding carfilzomib, are eligible)
Refractory to lenalidamide
Measurable disease with at least 1 of the following assessed within 28 days prior to enrollment:
Must have at least a PR to at least 1 line of prior therapy
Prior therapy with proteasome inhibitors is allowed. Subjects receiving prior carfilzomib therapy must have achieved at least a PR, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval from their last dose of carfilzomib
ECOG PS of 0 to 2
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35249 | United States | ||
| Rocky Mountain Cancer Centers Denver Midtown |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38497533 | Background | Perrot A, Delimpasi S, Spanoudakis E, Frolund U, Belotti A, Oriol A, Moreau P, McFadden I, Xia Q, Arora M, Dimopoulos MA. An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study. Leuk Lymphoma. 2024 Jun;65(6):833-842. doi: 10.1080/10428194.2024.2322030. Epub 2024 Mar 18. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
Participants with relapsed multiple myeloma whose disease was refractory to lenalidomide were enrolled.
Participants were enrolled at 25 study centers in Denmark, France, Germany, Greece, Italy, Spain, and the United States from 06 August 2020 to 01 October 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Carfilzomib With Pomalidomide and Dexamethasone (KPd) | Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study. Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study. Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Pre-assignment Period |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 16, 2022 | Oct 18, 2023 |
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| Dexamethasone | Drug | Dexamethasone will be administered at least 30 minutes, but no more than 4 hours prior to carfilzomib on days of carfilzomib administration. Dexamethasone will be administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle up to progression during cycles 1 to 12. Dexamethasone will be administered at a dose of 20 mg on days 1 and 15 of each 28-day cycle up to progression during cycles 13 onward. For subjects more than or equal to 75 years of age, the dose will be 20 mg during cycles 1 through 12 and 10 mg from cycles 13 onward. |
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| Pomalidomide | Drug | Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression. |
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| Day 1 cycle 1 to month 12 (8 to 13 month window) |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as events with onset on or after the administration of the first dose of any study treatment and within the end of study, or 30 days after the last dose of any study treatment, whichever one was earlier, excluding events reported after end of study date. | From the first dose of any study treatment until the end of study or 30 days after the last dose of any study treatment, whichever occured earlier; Median (min, max) was 8.5 (1.0, 46.6) months |
| Number of Participants Achieving MRD[-] Response | MRD[-] response was defined as achievement of MRD[-] status using next generation sequencing (NGS) based method in the bone marrow at any time. | From day 1 cycle 1 until the end of study (EOS); the mean duration of KPd treatment as of the EOS was 55.3 weeks |
| Number of Participants With Sustained MRD[-]CR for at Least 12 Months as Assessed by the IRC | MRD[-]CR at the 12 months landmark was defined as achievement of CR (including sCR or better) per IMWG-URC by IRC and MRD[-] status at a sensitivity of 10^-5 using NGS based method in the bone marrow at the 12 months landmark (from 8 months to 13 months window). Maintaining MRD[-]CR for at least 12 months (- 4 weeks) was considered as sustained. | Day 1 cycle 1 to month 12 (8 to 13 month window) |
| Number of Participants With Sustained MRD[-]CR at Month 24 as Assessed by the IRC | Sustained MRD[-]CR at 24 months included participants that maintained MRD[-]CR for 12 months or more after achieving MRD[-]CR status at 12 months. | Day 1 cycle 1 to month 26 (19 to 26 month window) |
| Kaplan-Meier Estimate of Duration of Response as Assessed by the IRC | Disease response and progression were determined using IMWG-URC. Durations were calculated for responders. Medians and percentiles were estimated using the Kaplan-Meier method. 90% CIs for medians and percentiles were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
| Time to Response as Assessed by the IRC | Durations were calculated for responders. Time to response was defined as the time from start of any study treatment date to the earliest date when confirmed sCR, CR, very good partial response (VGPR), or partial response (PR) was first achieved. | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
| Kaplan-Meier Estimate of Progression Free Survival (PFS) as Assessed by the IRC | PFS was defined as time from start of treatment until progression or death from any cause. Medians and percentiles were estimated using the Kaplan-Meier method by Klein and Moeschberger (1997). 90% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
| Kaplan-Meier Estimate of Overall Survival (OS) | OS was defined as the time from the start of treatment until death from any cause. Medians and percentiles were estimated using the Kaplan-Meier method. 90% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. | From day 1 cycle 1 until the EOS; the mean duration of KPd treatment was 55.3 weeks. |
| Number of Participants With Best Overall Confirmed Response of CR or Better as Assessed by the IRC | The number of safety analysis set participants whose best overall response was sCR or CR per IMWG-URC over the duration of the study. | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
| Denver |
| Colorado |
| 80218 |
| United States |
| Yale Cancer Center | New Haven | Connecticut | 06510 | United States |
| Affiliated Oncologists, LLC | Chicago Ridge | Illinois | 60415 | United States |
| Minnesota Oncology Hematology PA | Saint Paul | Minnesota | 55102 | United States |
| Oncology Hematology Care Incorporated | Cincinnati | Ohio | 45236 | United States |
| Texas Oncology - Austin Midtown | Austin | Texas | 78705 | United States |
| United States Oncology Regulatory Affairs Corporate Office | Austin | Texas | 78705 | United States |
| US Oncology Research Investigational Products Center | Austin | Texas | 78705 | United States |
| Baylor Charles A Sammons Cancer Center at Dallas | Dallas | Texas | 75246 | United States |
| Texas Oncology, Fort Worth | Fort Worth | Texas | 76104 | United States |
| Texas Oncology- Tyler | Tyler | Texas | 75702 | United States |
| Blue Ridge Cancer Care | Roanoke | Virginia | 24014 | United States |
| Aalborg Universitetshospital | Aalborg | 9000 | Denmark |
| Aarhus Universitetshospital | Aarhus N | 8200 | Denmark |
| Sjaellands Universitetshospital | Roskilde | 4000 | Denmark |
| Vejle Sygehus | Vejle | 7100 | Denmark |
| North Estonia Medical Centre | Tallinn | 13419 | Estonia |
| CHU Grenoble Alpes | Grenoble | 38043 | France |
| Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez | Lille | 59037 | France |
| Centre Hospitalier Universitaire de Nantes | Nantes | 44093 | France |
| Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut Lévêque | Pessac | 33604 | France |
| Centre Hospitalier de Saint Quentin | Saint-Quentin | 02321 | France |
| Clinique Sainte Anne | Strasbourg | 67000 | France |
| Institut Universitaire du Cancer Toulouse Oncopole | Toulouse | 31059 | France |
| Klinikum Chemnitz gGmbH | Chemnitz | 09113 | Germany |
| Asklepios Klinik Altona | Hamburg | 22763 | Germany |
| Universitätsklinikum Münster | Münster | 48149 | Germany |
| Universitatsklinikum Tubingen | Tübingen | 72076 | Germany |
| University General Hospital of Evros-Alexandroupolis District | Alexandroupoli | 68100 | Greece |
| General Hospital Evangelismos | Athens | 10676 | Greece |
| Alexandra Hospital | Athens | 11528 | Greece |
| University Hospital of Ioannina | Ioannina | 45500 | Greece |
| General University Hospital of Patras Panagia i Voithia | Pátrai | 26504 | Greece |
| Theagenion Cancer Hospital of Thessaloniki | Thessaloniki | 54007 | Greece |
| General Hospital of Thessaloniki Georgios Papanikolaou | Thessaloniki | 57010 | Greece |
| Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona | Ancona | 60126 | Italy |
| Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia | Brescia | 25123 | Italy |
| Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II | Lecce | 73100 | Italy |
| Policlinico Universitario Agostino Gemelli | Roma | 00168 | Italy |
| Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette | Torino | 10126 | Italy |
| Hospital Clinico Universitario de Salamanca | Salamanca | Castille and León | 37007 | Spain |
| Hospital Universitari Germans Trias i Pujol | Badalona | Catalonia | 08916 | Spain |
| Hospital Clinic i Provincial de Barcelona | Barcelona | Catalonia | 08036 | Spain |
| Hospital Universitari i Politecnic La Fe | Valencia | Valencia | 46026 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| COMPLETED |
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| NOT COMPLETED |
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| Treatment Period |
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Baseline measures are presented for the safety analysis set which included participants who received at least 1 dose of carfilzomib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Carfilzomib With Pomalidomide and Dexamethasone (KPd) | Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study. Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study. Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC) | Overall response was defined as the best overall confirmed response of: Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to < 200 mg/24-h. Assessment was by IRC per International Myeloma Working Group Uniform Response Criteria (IMWG-URC). The 90% confidence intervals were estimated using the Clopper-Pearson method (1994). | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Number | 90% Confidence Interval | percentage of participants | From day 1 cycle 1 until the primary analysis (PA) data cutoff (DCO); the mean duration of KPd treatment as of the DCO was 42.0 weeks |
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| Secondary | Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC | The MRD[-]CR rate was defined as the percentage of participants who reached MRD[-]CR at the 12 month landmark (8- to 13-month window). MRD[-]CR was defined as the achievement of CR (including sCR or better) per IMWG-URC by IRC assessment and MRD[-] status at a sensitivity of 10^-5 using next-generation sequencing based method in the bone marrow. The 90% CIs were estimated using the Clopper-Pearson method (1994). | The safety analysis set included all participants who received at least 1 dose of carfilzomib. The analysis was pre-specified until PA DCO only. | Posted | Number | 90% Confidence Interval | percentage of participants | Day 1 cycle 1 to month 12 (8 to 13 month window) |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as events with onset on or after the administration of the first dose of any study treatment and within the end of study, or 30 days after the last dose of any study treatment, whichever one was earlier, excluding events reported after end of study date. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Count of Participants | Participants | From the first dose of any study treatment until the end of study or 30 days after the last dose of any study treatment, whichever occured earlier; Median (min, max) was 8.5 (1.0, 46.6) months |
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| Secondary | Number of Participants Achieving MRD[-] Response | MRD[-] response was defined as achievement of MRD[-] status using next generation sequencing (NGS) based method in the bone marrow at any time. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Count of Participants | Participants | From day 1 cycle 1 until the end of study (EOS); the mean duration of KPd treatment as of the EOS was 55.3 weeks |
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| Secondary | Number of Participants With Sustained MRD[-]CR for at Least 12 Months as Assessed by the IRC | MRD[-]CR at the 12 months landmark was defined as achievement of CR (including sCR or better) per IMWG-URC by IRC and MRD[-] status at a sensitivity of 10^-5 using NGS based method in the bone marrow at the 12 months landmark (from 8 months to 13 months window). Maintaining MRD[-]CR for at least 12 months (- 4 weeks) was considered as sustained. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Count of Participants | Participants | Day 1 cycle 1 to month 12 (8 to 13 month window) |
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| Secondary | Number of Participants With Sustained MRD[-]CR at Month 24 as Assessed by the IRC | Sustained MRD[-]CR at 24 months included participants that maintained MRD[-]CR for 12 months or more after achieving MRD[-]CR status at 12 months. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Count of Participants | Participants | Day 1 cycle 1 to month 26 (19 to 26 month window) |
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| Secondary | Kaplan-Meier Estimate of Duration of Response as Assessed by the IRC | Disease response and progression were determined using IMWG-URC. Durations were calculated for responders. Medians and percentiles were estimated using the Kaplan-Meier method. 90% CIs for medians and percentiles were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. Only participants who achieved a partial response or better were included in the analysis. | Posted | Median | 90% Confidence Interval | months | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
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| Secondary | Time to Response as Assessed by the IRC | Durations were calculated for responders. Time to response was defined as the time from start of any study treatment date to the earliest date when confirmed sCR, CR, very good partial response (VGPR), or partial response (PR) was first achieved. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. Only participants who achieved a partial response or better were included in the analysis. | Posted | Median | Full Range | months | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
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| Secondary | Kaplan-Meier Estimate of Progression Free Survival (PFS) as Assessed by the IRC | PFS was defined as time from start of treatment until progression or death from any cause. Medians and percentiles were estimated using the Kaplan-Meier method by Klein and Moeschberger (1997). 90% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Median | 90% Confidence Interval | months | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
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| Secondary | Kaplan-Meier Estimate of Overall Survival (OS) | OS was defined as the time from the start of treatment until death from any cause. Medians and percentiles were estimated using the Kaplan-Meier method. 90% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Median | 90% Confidence Interval | months | From day 1 cycle 1 until the EOS; the mean duration of KPd treatment was 55.3 weeks. |
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| Secondary | Number of Participants With Best Overall Confirmed Response of CR or Better as Assessed by the IRC | The number of safety analysis set participants whose best overall response was sCR or CR per IMWG-URC over the duration of the study. | The safety analysis set included all participants who received at least 1 dose of carfilzomib. | Posted | Count of Participants | Participants | From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks |
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All-cause mortality: from enrollment until the end of study or death date, whichever occurs later; Median (min, max) time on study was 15.2 (0.0, 47.0) months. Adverse events: from the first dose of any study treatment until the end of study or 30 days after the last dose of any study treatment, whichever occurs earlier; Median (min, max) was 8.5 (1.0, 46.6) months
All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Carfilzomib With Pomalidomide and Dexamethasone (KPd) | Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study. Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study. Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study. | 37 | 54 | 22 | 52 | 48 | 52 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
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| Cardiac failure chronic | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
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| Left ventricular failure | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 27.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| COVID-19 pneumonia | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| Clostridium difficile infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| Cytomegalovirus infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Osteitis | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Renal disorder | Renal and urinary disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 27.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 7, 2022 | Oct 18, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012008 | Recurrence |
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C524865 | carfilzomib |
| D003907 | Dexamethasone |
| D002123 | Calcium Dobesilate |
| C467566 | pomalidomide |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
Not provided
Not provided
| Unknown or Not Reported |
|
| White |
|
| Other |
|
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