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

Phase 2

Completed

Conditions: Relapsed or Refractory Multiple Myeloma

Interventions: Drug: Carfilzomib
Drug: Dexamethasone
Drug: Pomalidomide

Registration Number: NCT04191616

Lead Sponsor: Amgen

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Carfilzomib combined with pomalidomide and dexamethasone	Pomalidomide	Carfilzomib, pomalidomide, and dexamethasone (KPd)
Carfilzomib combined with pomalidomide and dexamethasone	Carfilzomib	Carfilzomib, pomalidomide, and dexamethasone (KPd)
Carfilzomib combined with pomalidomide and dexamethasone	Dexamethasone	Carfilzomib, pomalidomide, and dexamethasone (KPd)

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC) (PA DCO Only)	From day 1 cycle 1 until the PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 weeks.	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Sustained MRD[-]CR at Month 24 as Assessed by the IRC	Day 1 cycle 1 to month 26 (19 to 26 month window)
Number of Participants Achieving Minimal Residual Disease Negative MRD[-] Response	Day 1 cycle 1 to month 60
Kaplan-Meier Estimate of Overall Survival	Day 1 cycle 1 to month 60
Number of Participants With Treatment-emergent Adverse Events	Day 1 cycle 1 up to approximately 60 months
Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC (PA DCO Only)	Day 1 cycle 1 to month 12 (8 to 13 month window). PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 weeks.	The MRD\[-\]CR rate was defined as the number 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).
Time to Response as Assessed by the IRC	Day 1 cycle 1 to month 60
Kaplan-Meier Estimate of Progression Free Survival as Assessed by the IRC	Day 1 cycle 1 to month 60
Number of Participants With Sustained MRD[-]CR for at Least 12 Months as Assessed by the IRC	Day 1 cycle 1 to month 60
Kaplan-Meier Estimate of Duration of Response as Assessed by the IRC	Day 1 cycle 1 to month 60
Number of Participants With Best Overall Confirmed Response of CR or Better as Assessed by the IRC	Day 1 cycle 1 to month 60

Trial Locations

Locations (46): Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez
🇫🇷
Lille Cedex, France
University Hospital of Ioannina
🇬🇷
Ioannina, Greece
Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II
🇮🇹
Lecce, Italy
Hospital Universitari i Politecnic La Fe
🇪🇸
Valencia, Comunidad Valenciana, Spain
North Estonia Medical Centre
🇪🇪
Tallinn, Estonia
General Hospital Evangelismos
🇬🇷
Athens, Greece
Theagenion Cancer Hospital of Thessaloniki
🇬🇷
Thessaloniki, Greece
General University Hospital of Patras Panagia i Voithia
🇬🇷
Patra, Greece
Aarhus Universitetshospital
🇩🇰
Aarhus N, Denmark
Sjaellands Universitetshospital
🇩🇰
Roskilde, Denmark
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Rocky Mountain Cancer Centers Denver Midtown
🇺🇸
Denver, Colorado, United States
Oncology Hematology Care Incorporated
🇺🇸
Cincinnati, Ohio, United States
Affiliated Oncologists, LLC
🇺🇸
Chicago Ridge, Illinois, United States
Minnesota Oncology Hematology PA
🇺🇸
Saint Paul, Minnesota, United States
Baylor Charles A Sammons Cancer Center at Dallas
🇺🇸
Dallas, Texas, United States
Texas Oncology, Fort Worth
🇺🇸
Fort Worth, Texas, United States
Aalborg Universitetshospital
🇩🇰
Aalborg, Denmark
Blue Ridge Cancer Care
🇺🇸
Roanoke, Virginia, United States
Vejle Sygehus
🇩🇰
Vejle, Denmark
CHU Grenoble Alpes
🇫🇷
Grenoble Cedex 9, France
Centre Hospitalier de Saint Quentin
🇫🇷
Saint Quentin, France
Clinique Sainte Anne
🇫🇷
Strasbourg, France
Centre Hospitalier Universitaire de Nantes
🇫🇷
Nantes Cedex 1, France
Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut Lévêque
🇫🇷
Pessac Cedex, France
Asklepios Klinik Altona
🇩🇪
Hamburg, Germany
Universitatsklinikum Tubingen
🇩🇪
Tubingen, Germany
Klinikum Chemnitz gGmbH
🇩🇪
Chemnitz, Germany
Institut Universitaire du Cancer Toulouse Oncopole
🇫🇷
Toulouse cedex 9, France
University General Hospital of Evros-Alexandroupolis District
🇬🇷
Alexandroupoli, Greece
Universitätsklinikum Münster
🇩🇪
Münster, Germany
Alexandra Hospital
🇬🇷
Athens, Greece
General Hospital of Thessaloniki Georgios Papanikolaou
🇬🇷
Thessaloniki, Greece
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
🇮🇹
Brescia, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
🇮🇹
Ancona, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹
Roma, Italy
Hospital Clinico Universitario de Salamanca
🇪🇸
Salamanca, Castilla León, Spain
Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette
🇮🇹
Torino, Italy
Hospital Clinic i Provincial de Barcelona
🇪🇸
Barcelona, Cataluña, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸
Badalona, Cataluña, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Texas Oncology- Tyler
🇺🇸
Tyler, Texas, United States
Yale Cancer Center
🇺🇸
New Haven, Connecticut, United States
Texas Oncology - Austin Midtown
🇺🇸
Austin, Texas, United States
United States Oncology Regulatory Affairs Corporate Office
🇺🇸
Austin, Texas, United States
US Oncology Research Investigational Products Center
🇺🇸
Austin, Texas, United States