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

NCT ID: NCT04191616

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-06
• Study Completion Date: 2024-10-01

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.

Conditions

Relapsed or Refractory Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carfilzomib combined with pomalidomide and dexamethasone

Carfilzomib, pomalidomide, and dexamethasone (KPd)

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: 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.

Dexamethasone

Intervention Type: 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.

Pomalidomide

Intervention Type: DRUG

Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Pomalidomide

Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression.

Intervention Type: DRUG

Other Intervention Names

Kyprolis; Decadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, Maxidex; Pomalyst

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Rocky Mountain Cancer Centers Denver Midtown

Denver, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Affiliated Oncologists, LLC

Chicago Ridge, Illinois, United States

Minnesota Oncology Hematology PA

Saint Paul, Minnesota, United States

Oncology Hematology Care Incorporated

Cincinnati, Ohio, 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

Baylor Charles A Sammons Cancer Center at Dallas

Dallas, Texas, United States

Texas Oncology, Fort Worth

Fort Worth, Texas, United States

Texas Oncology- Tyler

Tyler, Texas, United States

Blue Ridge Cancer Care

Roanoke, Virginia, United States

Aalborg Universitetshospital

Aalborg, , Denmark

Aarhus Universitetshospital

Aarhus N, , Denmark

Sjaellands Universitetshospital

Roskilde, , Denmark

Vejle Sygehus

Vejle, , Denmark

North Estonia Medical Centre

Tallinn, , Estonia

CHU Grenoble Alpes

Grenoble, , France

Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez

Lille, , France

Centre Hospitalier Universitaire de Nantes

Nantes, , France

Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut Lévêque

Pessac, , France

Centre Hospitalier de Saint Quentin

Saint-Quentin, , France

Clinique Sainte Anne

Strasbourg, , France

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, , France

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Asklepios Klinik Altona

Hamburg, , Germany

Universitätsklinikum Münster

Münster, , Germany

Universitatsklinikum Tubingen

Tübingen, , Germany

University General Hospital of Evros-Alexandroupolis District

Alexandroupoli, , Greece

General Hospital Evangelismos

Athens, , Greece

Alexandra Hospital

Athens, , Greece

University Hospital of Ioannina

Ioannina, , Greece

General University Hospital of Patras Panagia i Voithia

Pátrai, , Greece

Theagenion Cancer Hospital of Thessaloniki

Thessaloniki, , Greece

General Hospital of Thessaloniki Georgios Papanikolaou

Thessaloniki, , Greece

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, , Italy

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brescia, , Italy

Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II

Lecce, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette

Torino, , Italy

Hospital Clinico Universitario de Salamanca

Salamanca, Castille and León, Spain

Hospital Universitari Germans Trias i Pujol

Badalona, Catalonia, Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, Spain

Hospital Universitari i Politecnic La Fe

Valencia, Valencia, Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Countries

United States; Denmark; Estonia; France; Germany; Greece; Italy; Spain

References

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.

Reference Type: BACKGROUND

PMID: 38497533 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2019-001169-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20180117

Identifier Type: -

Identifier Source: org_study_id