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

NCT ID: NCT03859427

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 454 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-08
• Study Completion Date: 2023-03-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carfilzomib once-weekly

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

Group Type: ACTIVE_COMPARATOR

Carfilzomib

Intervention Type: 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.

Lenalidomide

Intervention Type: 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

Dexamethasone

Intervention Type: 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 twice-weekly

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

Group Type: ACTIVE_COMPARATOR

Carfilzomib

Intervention Type: DRUG

Twice weekly IV over 10 minutes on day 1, 2, 8, 9, 15 and 16 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 27 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.

Lenalidomide

Intervention Type: 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

Dexamethasone

Intervention Type: 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

Interventions

Carfilzomib

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.

Intervention Type: DRUG

Carfilzomib

Twice weekly IV over 10 minutes on day 1, 2, 8, 9, 15 and 16 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 27 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.

Intervention Type: DRUG

Lenalidomide

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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.

• 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

Robert A Moss Oncology

Fountain Valley, California, United States

Rocky Mountain Cancer Centers Denver Midtown

Denver, Colorado, United States

Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut

Plainville, Connecticut, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

New York Oncology Hematology, PC

Albany, New York, United States

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

Texas Oncology-Denton

Denton, Texas, United States

US Oncology Research Investigational Products Center

Fort Worth, Texas, United States

Oncology Consultants PA

Houston, Texas, United States

Texas Oncology

San Antonio, Texas, United States

United States Oncology Regulatory Affairs Corporate Office

The Woodlands, Texas, United States

Universitaetsklinikum Salzburg

Salzburg, , Austria

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD

Sofia, , Bulgaria

Specialized Hospital for Active Treatment of Hematology Diseases EAD

Sofia, , Bulgaria

Fakultni nemocnice Brno

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Helsingin Yliopistollinen Keskussairaala

Helsinki, , Finland

Oulun Yliopistollinen Sairaala

Oulu, , Finland

Turun Yliopistollinen Keskussairaala

Turku, , Finland

Centre Hospitalier Universitaire de Nantes

Nantes, , France

Centre Hospitalier Universitaire Archet 2

Nice, , France

Hopital Saint Louis

Paris, , France

Hopital Pitie-Salpetriere

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie

Poitiers, , France

Centre Hospitalier Universitaire de Rennes

Rennes, , France

Institut de Cancerologie Strasbourg

Strasbourg, , France

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, , France

Centre Hospitalier Universitaire de Nancy - Hopital de Brabois

Vandœuvre-lès-Nancy, , France

Charité, Universitätsklinikum Berlin, Campus Benjamin Franklin

Berlin, , Germany

Universitatsklinikum Koln

Cologne, , Germany

Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

Dresden, , Germany

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Johannes Gutenberg Universitaet Mainz

Mainz, , Germany

University Hospital of Alexandroupolis

Alexandroupoli, , Greece

General Hospital Evangelismos

Athens, , Greece

Agios Savvas Anticancer Hospital

Athens, , Greece

251 General Airforce Hospital

Athens, , Greece

Alexandra Hospital

Athens, , Greece

Metropolitan Hospital

Athens, , 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

Nagoya City University Hospital

Nagoya, Aichi-ken, Japan

Toyohashi Municipal Hospital

Toyohashi, Aichi-ken, Japan

Tesshokai Kameda General Hospital

Kamogawa-shi, Chiba, Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, Japan

Ogaki Municipal Hospital

Ogaki-shi, Gifu, Japan

National Hospital Organization Shibukawa Medical Center

Shibukawa-shi, Gunma, Japan

Japanese Red Cross Society Himeji Hospital

Himeji-shi, Hyōgo, Japan

Hyogo College of Medicine Hospital

Nishinomiya-shi, Hyōgo, Japan

Hitachi Ltd Hitachi General Hospital

Hitachi-shi, Ibaraki, Japan

University Hospital Kyoto Prefectural University of Medicine

Kyoto, Kyoto, Japan

National Hospital Organization Sendai Medical Center

Sendai, Miyagi, Japan

Niigata Cancer Center Hospital

Niigata, Niigata, Japan

National Hospital Organization Okayama Medical Center

Okayama, Okayama-ken, Japan

Japanese Red Cross Osaka Hospital

Osaka, Osaka, Japan

Kindai University Hospital

Osakasayama-shi, Osaka, Japan

Osaka University Hospital

Suita-shi, Osaka, Japan

Saitama Medical Center

Kawagoe-shi, Saitama, Japan

Tochigi Cancer Center

Utsunomiya, Tochigi, Japan

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, Japan

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, Japan

Hospital of Lithuanian University of Health Sciences Kaunas Clinics Public Institution

Kaunas, , Lithuania

Vilnius University Hospital Santaros Clinic Public Institution

Vilnius, , Lithuania

VU Medisch Centrum

Amsterdam, , Netherlands

Gelre Ziekenhuizen

Apeldoorn, , Netherlands

Spaarne Gasthuis

Hoofddorp, , Netherlands

Spitalul Clinic Colentina

Bucharest, , Romania

Fundeni Clinical Institute

Bucharest, , Romania

Institutul Clinic Fundeni

Bucharest, , Romania

Spitalul Clinic Coltea

Bucharest, , Romania

Spitalul Universitar de Urgenta Bucuresti

Bucharest, , Romania

Institutul Oncologic Prof Dr Ion Chiricuta

Cluj-Napoca, , Romania

Institutul Regional de Oncologie Iasi

Iași, , Romania

Spitalul Clinic Dr Gavril Curteanu Oradea

Oradea, , Romania

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, , Romania

Spitalul Clinic Municipal de Urgenta Timisoara

Timișoara, , Romania

Regional Clinical Hospital

Krasnoyarsk, , Russia

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

Moscow, , Russia

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

Moscow, , Russia

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

Petrozavodsk, , Russia

Federal centre of heart, blood and endocrinology Almazova

Saint Petersburg, , Russia

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

Samara, , Russia

Univerzitna nemocnica Bratislava, Nemocnica sv Cyrila a Metoda

Bratislava, , Slovakia

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, Spain

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 Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, Spain

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Falu Lasarett

Falun, , Sweden

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Hallands Sjukhus Halmstad

Halmstad, , Sweden

Sunderby Sjukhus

Luleå, , Sweden

Skanes Universitetssjukhus

Lund, , Sweden

Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi

Ankara, , Turkey (Türkiye)

Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi

Ankara, , Turkey (Türkiye)

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, , Turkey (Türkiye)

Bagcilar Medipol Mega Universite Hastanesi

Istanbul, , Turkey (Türkiye)

Istanbul Florence Nightingale Hastanesi

Istanbul, , Turkey (Türkiye)

Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi

Izmir, , Turkey (Türkiye)

Erciyes Universitesi Tip Fakultesi Mehmet Kemal Dedeman Hematoloji-Onkoloji Hastanesi

Kayseri, , Turkey (Türkiye)

Countries

United States; Austria; Bulgaria; Czechia; Finland; France; Germany; Greece; Japan; Lithuania; Netherlands; Romania; Russia; Slovakia; Spain; Sweden; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 39024542 (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

20180015

Identifier Type: -

Identifier Source: org_study_id