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

NCT04191616 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 201801172019-001169-34
• Study Type: interventional
• Target: 54
• Locations: 7 countries
• Sites: 45

Brief Summary

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

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

Multiple Myeloma; RRMM; Open-label; First Relapse Multiple Myeloma; Second Relapse Multiple Myeloma; Refractory to Lenalidomide; Triplicate Treatment Regimen; Dexamethasone; Carfilzomib; Pomalidomide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC

  Day 1 cycle 1 to month 12 (8 to 13 month window)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  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

  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

  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

  Day 1 cycle 1 to month 26 (19 to 26 month window)

Study Arms (1)

Carfilzomib combined with pomalidomide and dexamethasone

EXPERIMENTAL

Carfilzomib, pomalidomide, and dexamethasone (KPd)

Drug: Carfilzomib; Drug: Dexamethasone; Drug: Pomalidomide

Interventions

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.

Also known as: Kyprolis

Carfilzomib combined with pomalidomide and dexamethasone

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.

Also known as: Decadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, Maxidex

Carfilzomib combined with pomalidomide and dexamethasone

Pomalidomide DRUG

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

Also known as: Pomalyst

Carfilzomib combined with pomalidomide and dexamethasone

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (46)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Rocky Mountain Cancer Centers Denver Midtown

Denver, Colorado, 80218, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Affiliated Oncologists, LLC

Chicago Ridge, Illinois, 60415, United States

Location

Minnesota Oncology Hematology PA

Saint Paul, Minnesota, 55102, United States

Location

Oncology Hematology Care Incorporated

Cincinnati, Ohio, 45236, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

United States Oncology Regulatory Affairs Corporate Office

Austin, Texas, 78705, United States

Location

US Oncology Research Investigational Products Center

Austin, Texas, 78705, United States

Location

Baylor Charles A Sammons Cancer Center at Dallas

Dallas, Texas, 75246, United States

Location

Texas Oncology, Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Oncology- Tyler

Tyler, Texas, 75702, United States

Location

Blue Ridge Cancer Care

Roanoke, Virginia, 24014, United States

Location

Aalborg Universitetshospital

Aalborg, 9000, Denmark

Location

Aarhus Universitetshospital

Aarhus N, 8200, Denmark

Location

Sjaellands Universitetshospital

Roskilde, 4000, Denmark

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

North Estonia Medical Centre

Tallinn, 13419, Estonia

Location

CHU Grenoble Alpes

Grenoble, 38043, France

Location

Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, 44093, France

Location

Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut Lévêque

Pessac, 33604, France

Location

Centre Hospitalier de Saint Quentin

Saint-Quentin, 02321, France

Location

Clinique Sainte Anne

Strasbourg, 67000, France

Location

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059, France

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Universitatsklinikum Tubingen

Tübingen, 72076, Germany

Location

University General Hospital of Evros-Alexandroupolis District

Alexandroupoli, 68100, Greece

Location

General Hospital Evangelismos

Athens, 10676, Greece

Location

Alexandra Hospital

Athens, 11528, Greece

Location

University Hospital of Ioannina

Ioannina, 45500, Greece

Location

General University Hospital of Patras Panagia i Voithia

Pátrai, 26504, Greece

Location

Theagenion Cancer Hospital of Thessaloniki

Thessaloniki, 54007, Greece

Location

General Hospital of Thessaloniki Georgios Papanikolaou

Thessaloniki, 57010, Greece

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, 60126, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

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

Lecce, 73100, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

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

Torino, 10126, Italy

Location

Hospital Clinico Universitario de Salamanca

Salamanca, Castille and León, 37007, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Catalonia, 08916, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Related Publications (1)

• 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.

  PMID: 38497533 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate; pomalidomide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2019
• First Posted: December 10, 2019
• Study Start: August 6, 2020
• Primary Completion: November 30, 2022
• Study Completion: October 1, 2024
• Last Updated: September 4, 2025
• Results First Posted: November 8, 2023

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

IT (5); US (13); ES (5); DE (4); DK (4); FR (7); GR (7)