A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

NCT03859427 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 20180015
• Study Type: interventional
• Target: 454
• Locations: 17 countries
• Sites: 108

Brief Summary

Compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with lenalidomide and dexamethasone (KRd 56 mg/m2) to 27 mg/m2 carfilzomib administered twice-weekly in combination with lenalidomide and dexamethasone (KRd 27 mg/m2) in subjects with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy.

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

Bone Marrow Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) Per International Myeloma Working Group Uniform Response Criteria (IMWG-URC)

  ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG-URC. CR: negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). sCR: CR and normal serum free light chain ratio and no clonal cells in BM by immunohistochemistry. VGPR: Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-hours). PR: ≥ 50% reduction of serum M-protein and reduction in 24-hours urinary M-protein by ≥ 90% or to \< 200 mg/24-hours. The ORR 95% confidence intervals (CIs) were estimated using the Clopper-Pearson method.

  Cycle 1 Day 1 up to approximately 12 months (cycle = 28 days); median treatment duration for the twice-weekly arm was 47.00 weeks and for the once-weekly arm was 47.14 weeks.

Secondary Outcomes (12)

• Kaplan-Meier Estimate of Progression-free Survival (PFS) Rate at 12 Months

  12 months

• Percentage of Participants Who Reported Convenience as Measured by the Patient-reported Convenience With Carfilzomib-dosing Schedule Question

  Day 28 of Cycle 4

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

  Cycle 1 Day 1 up to end of Cycle 12 + 30 days, where each cycle was 28 days; median treatment duration (any study treatment) was 47.00 weeks in the twice-weekly KRd group and 47.14 weeks in the once-weekly KRd group

• Time to Response (TTR)

  Cycle 1 Day 1 up to approximately 12 months (cycle = 28 days); median treatment duration for the twice-weekly arm was 47.00 weeks and for the once-weekly arm was 47.14 weeks.

• Kaplan-Meier Estimate of Duration of Response (DOR)

  Cycle 1 Day 1 up to approximately 12 months (cycle = 28 days); median treatment duration for the twice-weekly arm was 47.00 weeks and for the once-weekly arm was 47.14 weeks.

Study Arms (2)

Carfilzomib once-weekly

ACTIVE COMPARATOR

Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Carfilzomib twice-weekly

ACTIVE COMPARATOR

Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Once weekly IV over 30 minutes on day 1, 8 and 15 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 day 1 and 56 mg/m2 beginning with cycle 1 day 8 and thereafter. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent.

Carfilzomib once-weekly

Lenalidomide DRUG

Once daily orally 25 mg days 1 to 21 of each cycle. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent

Carfilzomib once-weekly; Carfilzomib twice-weekly

Dexamethasone DRUG

Once daily orally or by IV 40 mg days 1, 8 and 15 of each cycle. Also day 22 of cycles 1 to 9. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent

Carfilzomib once-weekly; Carfilzomib twice-weekly

Eligibility Criteria

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

You may qualify if:

• Multiple myeloma with documented relapse or progression after most recent myeloma treatment. Subjects refractory to the most recent line of therapy are eligible, unless last treatment contained proteasome inhibitor (PI) or lenalidomide and dexamethasone. Refractory is defined as disease that is nonresponsive or progresses within 60 days of last therapy.
• Subjects must have at least PR to at least 1 line of prior therapy.
• Subjects must have received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation maintenance therapy will be considered as 1 line of therapy).
• Prior therapy with a PI or the combination of lenalidomide and dexamethasone are allowed if the patient had at least a PR to the most recent treatment with a PI or lenalidomide and dexamethasone, neither PI or lenalidomide and dexamethasone containing treatment were ceased due to toxicity, the patient has not relapsed within 60 days of discontinuation of the PI or lenalidomide and dexamethasone containing treatment. A history of prior neuropathy is permitted if this was not grade 3, grade 4 or grade 2 with pain and if not resolved within the 14 days before enrollment, is less than or equal to grade 2 without pain. Patients are permitted to have received single agent lenalidomide as maintenance therapy within 60 days of enrollment.
• Previous treatment with a lenalidomide and dexamethasone containing regimen is allowed, as long as the subject did not progress during the first 3 months after initiating lenalidomide and dexamethasone containing therapy.
• Measurable disease with at least 1 of the following assessed within 21 days prior to randomization:
• Immunoglobulin G (IgG) multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
• Immunoglobulin A (IgA), Immunoglobulin D (IgD), Immunoglobulin E (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
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 ≤ 2

You may not qualify if:

• Waldenström macroglobulinemia.
• Multiple myeloma of Immunoglobulin M (IgM) subtype.
• Plasma cell leukemia (\> 2.0 × 10\^9 /L circulating plasma cells by standard differential).
• Uncontrolled hypertension, defined as a subject whose blood pressure is greater than or equal to 160 mmHg systolic or greater than or equal to 100 mmHg diastolic when taken in accordance with the European Society of Hypertension/European Society of Cardiology 2018 guidelines (Section 12.10; Williams et al, 2018).
• Active congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, screening ECG with corrected QT interval (QTc) of \> 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization.
• Calculated or measured creatinine clearance \< 30 mL/min (calculation must be based on the Cockcroft and Gault formula) within 28 days prior to randomization.

Sponsors & Collaborators

• Amgen: lead

Study Sites (108)

Robert A Moss Oncology

Fountain Valley, California, 92708, United States

Location

Rocky Mountain Cancer Centers Denver Midtown

Denver, Colorado, 80218, United States

Location

Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut

Plainville, Connecticut, 06062, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

Location

New York Oncology Hematology, PC

Albany, New York, 12208, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

Texas Oncology-Denton

Denton, Texas, 76201, United States

Location

US Oncology Research Investigational Products Center

Fort Worth, Texas, 76177, United States

Location

Oncology Consultants PA

Houston, Texas, 77030, United States

Location

Texas Oncology

San Antonio, Texas, 78229, United States

Location

United States Oncology Regulatory Affairs Corporate Office

The Woodlands, Texas, 77380, United States

Location

Universitaetsklinikum Salzburg

Salzburg, 5020, Austria

Location

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, 4002, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD

Sofia, 1431, Bulgaria

Location

Specialized Hospital for Active Treatment of Hematology Diseases EAD

Sofia, 1756, Bulgaria

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 775 20, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

Helsingin Yliopistollinen Keskussairaala

Helsinki, 00290, Finland

Location

Oulun Yliopistollinen Sairaala

Oulu, 90220, Finland

Location

Turun Yliopistollinen Keskussairaala

Turku, 20521, Finland

Location

Centre Hospitalier Universitaire de Nantes

Nantes, 44000, France

Location

Centre Hospitalier Universitaire Archet 2

Nice, 06202, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hopital Pitie-Salpetriere

Paris, 75013, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie

Poitiers, 86021, France

Location

Centre Hospitalier Universitaire de Rennes

Rennes, 35033, France

Location

Institut de Cancerologie Strasbourg

Strasbourg, 67033, France

Location

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059, France

Location

Centre Hospitalier Universitaire de Nancy - Hopital de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Charité, Universitätsklinikum Berlin, Campus Benjamin Franklin

Berlin, 12200, Germany

Location

Universitatsklinikum Koln

Cologne, 50924, Germany

Location

Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Universitatsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Johannes Gutenberg Universitaet Mainz

Mainz, 55131, Germany

Location

University Hospital of Alexandroupolis

Alexandroupoli, 68100, Greece

Location

General Hospital Evangelismos

Athens, 10676, Greece

Location

Agios Savvas Anticancer Hospital

Athens, 115 22, Greece

Location

251 General Airforce Hospital

Athens, 11525, Greece

Location

Alexandra Hospital

Athens, 11528, Greece

Location

Metropolitan Hospital

Athens, 18547, 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

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Toyohashi Municipal Hospital

Toyohashi, Aichi-ken, 441-8570, Japan

Location

Tesshokai Kameda General Hospital

Kamogawa-shi, Chiba, 296-8602, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, 811-1395, Japan

Location

Ogaki Municipal Hospital

Ogaki-shi, Gifu, 503-8502, Japan

Location

National Hospital Organization Shibukawa Medical Center

Shibukawa-shi, Gunma, 377-0280, Japan

Location

Japanese Red Cross Society Himeji Hospital

Himeji-shi, Hyōgo, 670-8540, Japan

Location

Hyogo College of Medicine Hospital

Nishinomiya-shi, Hyōgo, 663-8501, Japan

Location

Hitachi Ltd Hitachi General Hospital

Hitachi-shi, Ibaraki, 317-0077, Japan

Location

University Hospital Kyoto Prefectural University of Medicine

Kyoto, Kyoto, 602-8566, Japan

Location

National Hospital Organization Sendai Medical Center

Sendai, Miyagi, 983-8520, Japan

Location

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, Okayama-ken, 701-1192, Japan

Location

Japanese Red Cross Osaka Hospital

Osaka, Osaka, 543-8555, Japan

Location

Kindai University Hospital

Osakasayama-shi, Osaka, 589-8511, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Saitama Medical Center

Kawagoe-shi, Saitama, 350-8550, Japan

Location

Tochigi Cancer Center

Utsunomiya, Tochigi, 320-0834, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

Location

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, 150-8935, Japan

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics Public Institution

Kaunas, 50009, Lithuania

Location

Vilnius University Hospital Santaros Clinic Public Institution

Vilnius, 08661, Lithuania

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

Gelre Ziekenhuizen

Apeldoorn, 7334 DZ, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, 2134 TM, Netherlands

Location

Spitalul Clinic Colentina

Bucharest, 020125, Romania

Location

Fundeni Clinical Institute

Bucharest, 022328, Romania

Location

Institutul Clinic Fundeni

Bucharest, 022328, Romania

Location

Spitalul Clinic Coltea

Bucharest, 030171, Romania

Location

Spitalul Universitar de Urgenta Bucuresti

Bucharest, 050098, Romania

Location

Institutul Oncologic Prof Dr Ion Chiricuta

Cluj-Napoca, 400015, Romania

Location

Institutul Regional de Oncologie Iasi

Iași, 700483, Romania

Location

Spitalul Clinic Dr Gavril Curteanu Oradea

Oradea, 410469, Romania

Location

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, 550245, Romania

Location

Spitalul Clinic Municipal de Urgenta Timisoara

Timișoara, 300079, Romania

Location

Regional Clinical Hospital

Krasnoyarsk, 660022, Russia

Location

Moscow State Budget Healthcare Institution City clinical Hospital 52 of Moscow Healthcare Department

Moscow, 123182, Russia

Location

SBHI of Moscow city City clinical hospital na S P Botkin of Moscow city Healthcare department

Moscow, 125284, Russia

Location

SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov

Petrozavodsk, 185019, Russia

Location

Federal centre of heart, blood and endocrinology Almazova

Saint Petersburg, 197341, Russia

Location

State Budget Educational Institution of High Professional Skills Samara State Medical University

Samara, 443079, Russia

Location

Univerzitna nemocnica Bratislava, Nemocnica sv Cyrila a Metoda

Bratislava, 851 07, Slovakia

Location

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, 07010, Spain

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 Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Falu Lasarett

Falun, 791 82, Sweden

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, 413 45, Sweden

Location

Hallands Sjukhus Halmstad

Halmstad, 301 85, Sweden

Location

Sunderby Sjukhus

Luleå, 971 80, Sweden

Location

Skanes Universitetssjukhus

Lund, 221 85, Sweden

Location

Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi

Ankara, 06560, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi

Ankara, 06590, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, 34093, Turkey (Türkiye)

Location

Bagcilar Medipol Mega Universite Hastanesi

Istanbul, 34214, Turkey (Türkiye)

Location

Istanbul Florence Nightingale Hastanesi

Istanbul, 34387, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi

Izmir, 35340, Turkey (Türkiye)

Location

Erciyes Universitesi Tip Fakultesi Mehmet Kemal Dedeman Hematoloji-Onkoloji Hastanesi

Kayseri, 38039, Turkey (Türkiye)

Location

Related Publications (1)

• Dimopoulos MA, Coriu D, Delimpasi S, Spicka I, Upchurch T, Fang B, Talpur R, Faber E, Beksac M, Leleu X. A.R.R.O.W.2: once- vs twice-weekly carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma. Blood Adv. 2024 Oct 8;8(19):5012-5021. doi: 10.1182/bloodadvances.2024013101.

  PMID: 39024542 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Recurrence; Multiple Myeloma; Bone Marrow Neoplasms

Interventions

carfilzomib; Lenalidomide; Dexamethasone

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; Hematologic Neoplasms; Neoplasms by Site; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: March 1, 2019
• Study Start: May 8, 2019
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: August 13, 2024
• Results First Posted: April 18, 2024

Record last verified: 2024-08

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

DE (5); JP (21); BU (3); NL (3); FI (3); AU (1); ES (6); SL (1); RU (6); LI (2); GR (9); US (12); SE (5); CZ (4); FR (10); RO (10); TU (7)