Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet (SELECT)

An Open-label, Phase 2 Study Treating Subjects With First or Second Relapse of Multiple Myeloma With Carfilzomib, Pomalidomide, and Dexamethasone (KPd)

A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with Pomalidomide and Dexamethasone

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Carfilzomib; Drug: Dexamethasone; Drug: Pomalidomide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital
  • Roskilde, Denmark, 4000
    • Sjaellands Universitetshospital
  • Vejle, Denmark, 7100
    • Vejle Sygehus
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre
• France
  • Grenoble, France, 38043
    • Chu Grenoble Alpes
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire De Nantes
  • Pessac, France, 33604
    • Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque
  • Saint-Quentin, France, 02321
    • Centre Hospitalier de Saint Quentin
  • Strasbourg, France, 67000
    • Clinique Sainte Anne
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer Toulouse Oncopole
• Germany
  • Chemnitz, Germany, 09113
    • Klinikum Chemnitz gGmbH
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen
• Greece
  • Alexandroupoli, Greece, 68100
    • University General Hospital of Evros-Alexandroupolis District
  • Athens, Greece, 11528
    • Alexandra Hospital
  • Athens, Greece, 10676
    • General Hospital Evangelismos
  • Ioannina, Greece, 45500
    • University Hospital of Ioannina
  • Pátrai, Greece, 26504
    • General University Hospital of Patras Panagia i Voithia
  • Thessaloniki, Greece, 54007
    • Theagenion Cancer Hospital of Thessaloniki
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki Georgios Papanikolaou
• Italy
  • Ancona, Italy, 60126
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Lecce, Italy, 73100
    • Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli
  • Torino, Italy, 10126
    • Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Castille and León
    • Salamanca, Castille and León, Spain, 37007
      • Hospital Clínico Universitario de Salamanca
  • Catalonia
    • Badalona, Catalonia, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic i Provincial de Barcelona
  • Valencia
    • Valencia, Valencia, Spain, 46026
      • Hospital Universitari i Politecnic La Fe
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers Denver Midtown
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Illinois
    • Chicago Ridge, Illinois, United States, 60415
      • Affiliated Oncologists, LLC
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Minnesota Oncology Hematology PA
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Incorporated
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin Midtown
    • Austin, Texas, United States, 78705
      • United States Oncology Regulatory Affairs Corporate Office
    • Austin, Texas, United States, 78705
      • US Oncology Research Investigational Products Center
    • Dallas, Texas, United States, 75246
      • Baylor Charles A Sammons Cancer Center at Dallas
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, Fort Worth
    • Tyler, Texas, United States, 75702
      • Texas Oncology- Tyler
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

  • IgG multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
  • IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL
  • urine M-protein ≥ 200 mg per 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 serum kappa lambda ratio
• 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

• Primary refractory multiple myeloma
• Waldenström macroglobulinemia
• Multiple myeloma of IgM subtype
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia ( greater than 2.0 × 109/L circulating plasma cells by differential). If automated differential shows ≥ 20% of other cells, obtain manual differential to identify other cells.
• Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)
• Previous diagnosis of amyloidosis associated with myeloma
• Myelodysplastic syndrome
• Toxicity requiring discontinuation of lenalidomide therapy
• Prior treatment with pomalidomide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Carfilzomib combined with pomalidomide and dexamethasone; Carfilzomib, pomalidomide, and dexamethasone (KPd)

Drug: Carfilzomib; 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.; Other Names: Kyprolis; Drug: Dexamethasone; 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.; Other Names: Decadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, Maxidex; Drug: Pomalidomide; Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression.; Other Names: Pomalyst

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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).	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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): October 1, 2024

Study Registration Dates

• First Submitted: November 22, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Pomalidomide; Multiple Myeloma; Open-label; Dexamethasone; Carfilzomib; RRMM; First Relapse Multiple Myeloma; Second Relapse Multiple Myeloma; Refractory to Lenalidomide; Triplicate Treatment Regimen
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Multiple Myeloma; Sulfur Compounds; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Sulfonic Acids; Sulfur Acids; Pregnadienetriols; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Dexamethasone; Calcium Dobesilate; carfilzomib; pomalidomide
• Other Study ID Numbers: 20180117; 2019-001169-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No