A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (ARROW2)

A Randomized, Open-label, Phase 3 Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (A.R.R.O.W.2)

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.

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Carfilzomib; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 454
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Universitaetsklinikum Salzburg
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
  • Sofia, Bulgaria, 1756
    • Specialized Hospital for Active Treatment of Hematology Diseases EAD
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni Nemocnice Brno
  • Hradec Kralove, Czechia, 500 05
    • Fakultni Nemocnice Hradec Kralove
  • Olomouc, Czechia, 775 20
    • Fakultni Nemocnice Olomouc
  • Praha 2, Czechia, 128 08
    • Vseobecna Fakultni Nemocnice V Praze
• Finland
  • Helsinki, Finland, 00290
    • Helsingin Yliopistollinen Keskussairaala
  • Oulu, Finland, 90220
    • Oulun yliopistollinen sairaala
  • Turku, Finland, 20521
    • Turun yliopistollinen keskussairaala
• France
  • Nantes, France, 44000
    • Centre Hospitalier Universitaire de Nantes
  • Nice cedex 3, France, 06202
    • Centre Hospitalier Universitaire Archet 2
  • Paris, France, 75010
    • Hôpital Saint Louis
  • Paris, France, 75013
    • Hôpital Pitié-Salpétrière
  • Pierre-Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Poitiers Cedex, France, 86021
    • Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie
  • Rennes, France, 35033
    • Centre hospitalier universitaire de Rennes
  • Strasbourg, France, 67033
    • Institut de Cancerologie Strasbourg
  • Toulouse cedex 9, France, 31059
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Vandoeuvre les Nancy Cedex, France, 54511
    • Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois
• Germany
  • Berlin, Germany, 12200
    • Charité, Universitätsklinikum Berlin, Campus Benjamin Franklin
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Köln, Germany, 50924
    • Universitatsklinikum Koln
  • Mainz, Germany, 55131
    • Johannes Gutenberg Universitaet Mainz
• Greece
  • Alexandroupoli, Greece, 68100
    • University Hospital of Alexandroupolis
  • Athens, Greece, 18547
    • Metropolitan Hospital
  • Athens, Greece, 11528
    • Alexandra Hospital
  • Athens, Greece, 10676
    • General Hospital Evangelismos
  • Athens, Greece, 115 22
    • Agios Savvas Anticancer Hospital
  • Athens, Greece, 11525
    • 251 General Airforce Hospital
  • Patra, Greece, 26504
    • General University Hospital of Patras Panagia i Voithia
  • Thessaloniki, Greece, 54007
    • Theagenion Cancer Hospital of Thessaloniki
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki Georgios Papanikolaou
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
    • Toyohashi-shi, Aichi, Japan, 441-8570
      • Toyohashi Municipal Hospital
  • Chiba
    • Kamogawa-shi, Chiba, Japan, 296-8602
      • Tesshokai Kameda General Hospital
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
  • Gifu
    • Ogaki-shi, Gifu, Japan, 503-8502
      • Ogaki Municipal Hospital
  • Gunma
    • Shibukawa-shi, Gunma, Japan, 377-0280
      • National Hospital Organization Shibukawa Medical Center
  • Hyogo
    • Himeji-shi, Hyogo, Japan, 670-8540
      • Japanese Red Cross Society Himeji Hospital
    • Nishinomiya-shi, Hyogo, Japan, 663-8501
      • Hyogo College of Medicine Hospital
  • Ibaraki
    • Hitachi-shi, Ibaraki, Japan, 317-0077
      • Hitachi Ltd Hitachi General Hospital
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • University Hospital Kyoto Prefectural University of Medicine
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 983-8520
      • National Hospital Organization Sendai Medical Center
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8566
      • Niigata Cancer Center Hospital
  • Okayama
    • Okayama-shi, Okayama, Japan, 701-1192
      • National Hospital Organization Okayama Medical Center
  • Osaka
    • Osaka-shi, Osaka, Japan, 543-8555
      • Japanese Red Cross Osaka Hospital
    • Osakasayama-shi, Osaka, Japan, 589-8511
      • Kindai University Hospital
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Saitama
    • Kawagoe-shi, Saitama, Japan, 350-8550
      • Saitama Medical Center
  • Tochigi
    • Utsunomiya-shi, Tochigi, Japan, 320-0834
      • Tochigi Cancer Center
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Japanese Red Cross Medical Center
• Lithuania
  • Kaunas, Lithuania, 50009
    • Hospital of Lithuanian University of Health Sciences Kaunas Clinics Public Institution
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santaros Clinic Public Institution
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Apeldoorn, Netherlands, 7334 DZ
    • Gelre Ziekenhuizen
  • Hoofddorp, Netherlands, 2134 TM
    • Spaarne Gasthuis
• Romania
  • Bucharest, Romania, 022328
    • Fundeni Clinical Institute
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni
  • Bucharest, Romania, 030171
    • Spitalul Clinic Coltea
  • Bucharest, Romania, 050098
    • Spitalul Universitar de Urgenta Bucuresti
  • Bucuresti, Romania, 020125
    • Spitalul Clinic Colentina
  • Cluj-Napoca, Romania, 400015
    • Institutul Oncologic Prof Dr Ion Chiricuta
  • Iasi, Romania, 700483
    • Institutul Regional de Oncologie Iasi
  • Oradea, Romania, 410469
    • Spitalul Clinic Dr Gavril Curteanu Oradea
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean De Urgenta Sibiu
  • Timisoara, Romania, 300079
    • Spitalul Clinic Municipal de Urgenta Timisoara
• Russian Federation
  • Krasnoyarsk, Russian Federation, 660022
    • Regional Clinical Hospital
  • Moscow, Russian Federation, 123182
    • Moscow State Budget Healthcare Institution City clinical Hospital 52 of Moscow Healthcare Department
  • Moscow, Russian Federation, 125284
    • SBHI of Moscow city City clinical hospital na S P Botkin of Moscow city Healthcare department
  • Petrozavodsk, Russian Federation, 185019
    • SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov
  • Saint Petersburg, Russian Federation, 197341
    • Federal centre of heart, blood and endocrinology Almazova
  • Samara, Russian Federation, 443079
    • State Budget Educational Institution of High Professional Skills Samara State Medical University
• Slovakia
  • Bratislava, Slovakia, 851 07
    • Univerzitna nemocnica Bratislava, Nemocnica sv Cyrila a Metoda
• Spain
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07010
      • Hospital Universitari Son Espases
  • Castilla León
    • Salamanca, Castilla León, Spain, 37007
      • Hospital Clínico Universitario de Salamanca
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Barcelona, Cataluña, Spain, 08036
      • Hospital Clinic i Provincial de Barcelona
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra
• Sweden
  • Falun, Sweden, 791 82
    • Falu Lasarett
  • Goteborg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset
  • Halmstad, Sweden, 301 85
    • Hallands Sjukhus Halmstad
  • Lulea, Sweden, 971 80
    • Sunderby Sjukhus
  • Lund, Sweden, 221 85
    • Skanes universitetssjukhus
• Turkey
  • Ankara, Turkey, 06560
    • Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi
  • Ankara, Turkey, 06590
    • Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi
  • Istanbul, Turkey, 34093
    • Istanbul Universitesi Istanbul Tip Fakultesi
  • Istanbul, Turkey, 34214
    • Bagcilar Medipol Mega Universite Hastanesi
  • Istanbul, Turkey, 34387
    • Istanbul Florence Nightingale Hastanesi
  • Izmir, Turkey, 35340
    • Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi
  • Kayseri, Turkey, 38039
    • Erciyes Universitesi Tip Fakultesi Mehmet Kemal Dedeman Hematoloji-Onkoloji Hastanesi
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • Robert A Moss Oncology
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers Denver Midtown
  • Connecticut
    • Plainville, Connecticut, United States, 06062
      • Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, PC
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc
  • Texas
    • Denton, Texas, United States, 76201
      • Texas Oncology-Denton
    • Fort Worth, Texas, United States, 76177
      • US Oncology Research Investigational Products Center
    • Houston, Texas, United States, 77030
      • Oncology Consultants PA
    • San Antonio, Texas, United States, 78229
      • Texas Oncology
    • The Woodlands, Texas, United States, 77380
      • United States Oncology Regulatory Affairs Corporate Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Other inclusion criteria may apply

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.

Other exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Carfilzomib once-weekly; Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2	Drug: 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.; 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.; 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; 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
Active Comparator: Carfilzomib twice-weekly; Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2	Drug: 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.; 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.; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Estimate of Progression-free Survival (PFS) Rate at 12 Months	PFS rate was defined as the percentage of participants without disease progression or death due to any cause at 12 months. The PFS rate at 12 months was estimated using the Kaplan-Meier method by Klein and Moeschberger (1997). 95% CIs were estimated using the method by Kalbfleisch and Prentice (1980). PFS data was censored for participants who met any one of the following: 1. no baseline/no post-baseline disease assessments; 2. starting new anti-myeloma therapy before documentation of progressive disease (PD) or death; 3. PD or death immediately after more than 1 consecutively missed disease assessment visit (PD or death immediately after > 63 days without disease assessment visit); 4. alive without documentation of PD; 5. lost to follow-up or withdrawn consent.	12 months
Percentage of Participants Who Reported Convenience as Measured by the Patient-reported Convenience With Carfilzomib-dosing Schedule Question	Patient-reported convenience was measured by the Patient-reported Convenience with Carfilzomib-dosing Schedule Question. The items in the questionnaire were categorized as 'Convenient', which included responses of 'Very Convenient' and 'Convenient', and 'Inconvenient' which included responses of 'Inconvenient' and 'Very Inconvenient'. The 95% CIs were estimated using the Clopper-Pearson method.	Day 28 of Cycle 4
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs were AEs starting on or after the first dose of any study drug, and up to 30 days of the last dose of any study drug, excluding AEs reported after End of Study date.	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)	TTR was defined as the time from randomization to the earliest date when confirmed sCR, CR, VGPR, or PR per IMWG-URC was first achieved.	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)	For participants who achieved a PR or better, i.e., sCR, CR, VGPR, or PR per IMWG-URC, the DOR was defined as the time from the earliest date when a PR or better was first achieved, and subsequently confirmed, to the earliest date of confirmed PD or death due to any cause. Median DOR was estimated using the Kaplan-Meier method. 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. For those alive and who had not experienced PD by analysis time, DOR was censored for participants who met any one of the following: 1. no baseline/no post-baseline disease assessments; 2. starting new anti-myeloma therapy before documentation of PD or death; 3. PD or death immediately after more than 1 consecutively missed disease assessment visit (PD or death immediately after > 63 days without disease assessment visit); 4. alive without documentation of PD; 5. lost to follow-up or withdrawn consent.	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 Time to Progression (TTP)	TTP was defined as the duration from randomization for the first documented disease progression per IMWG-UCR. Median TTP was estimated using the Kaplan-Meier method. 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. TTP was censored for participants who had no confirmed PD at the last non non-evaluable (non-NE), post-baseline disease assessment or the earlier of the following, where applicable: 1. the last non-NE, post-baseline disease assessment prior to start of a new anti-myeloma treatment, or 2. the last non-NE, post-baseline assessment followed > 63 days later by disease progression; otherwise, at randomization.	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 Overall Survival (OS)	OS was defined as the time from randomization to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. Participants still alive or lost to follow-up or withdrawn consent from study by the analysis time were censored at the date on which the participant was last known to be alive.	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.
Percentage of Participants Who Achieved Minimal Residual Disease Negative Complete Response (MRD[-]CR) by Independent Review Committee (IRC) Per IMWG-URC	MRD[-]CR was defined as achievement of CR or better by IRC per IMWG-URC and achievement of MRD negativity as assessed by next generation sequencing method at a 10^-5 threshold over the duration of the study. The 95% CIs for percentages 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.
Percentage of Participants With Minimal Residual Disease Negativity (MRD[-]) by IRC Per IMWG-URC at 12 Months	The percentage of participants with achievement of MRD[-] at 12 months (± 4 weeks) from randomization, as assessed by next generation sequencing method at a 10^-5 threshold. MRD negativity results from BM samples obtained at 8 to 13 months from randomization and prior to new anti-myeloma therapy or disease progression were considered in the calculation. The 95% CIs for percentages were estimated using the Clopper-Pearson method.	Cycle 1 Day 1 up to 12 months (cycle = 28 days)
Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ)-Core 30 (C30) Physical Functioning Scale	The QLQ-C30 physical function is one of the functional domains of the EORTC QLQ-C30 self-reported instrument and the physical functioning score score ranges from 0-100 points, with 100 points indicating the best possible functioning. A positive change from baseline indicated an improvement in functioning.	Baseline (Cycle 1 Day 1), Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, Cycle 12 Day 1, and safety follow-up (30 days after last dose)
Change From Baseline in EORTC QLQ-C30 Role Functioning Scale	The QLQ-C30 role function is one of the functional domains of the EORTC QLQ-C30 self-reported instrument and the role functioning score ranges from 0-100 points, with 100 points indicating the best possible functioning. A positive change from baseline indicated an improvement in functioning.	Baseline (Cycle 1 Day 1), Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, Cycle 12 Day 1, and safety follow-up (30 days after last dose)
Patient-reported Treatment Satisfaction as Measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ)	The CTSQ measures treatment satisfaction in individuals with cancer and includes a domain for satisfaction with therapy. The satisfaction with therapy scores ranges from 0 to 100 points, with 100 points indicating greatest satisfaction. Analysis was based on ANCOVA model. The dependent variable of the models were the scale scores measured at each visit. The model included effects of intercept, scale score measured at cycle 2 day 1 visit, treatment arm, and randomization stratification factors.	Cycle 5 Day 1, Cycle 12 Day 1, and safety follow-up (30 days after last dose)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Bone Marrow Cancer
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide
• Other Study ID Numbers: 20180015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No