Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma.

Refractory Multiple Myeloma Clinical Trial

— CANDOR  

Official title:

A Randomized, Open-label, Phase 3 Study Comparing Carfilzomib, Dexamethasone, and Daratumumab to Carfilzomib and Dexamethasone for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03158688
• Other study ID #: 20160275
• Secondary ID: 2016-003554-33
• Status: Completed
• Phase: Phase 3
• Start date: June 13, 2017
• Est. completion date: April 15, 2022

Study information

• Verified date: March 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Compare carfizomib, dexamethasone, and daratumumab (KdD) to Carfilzomib and dexamethasone (Kd) in terms of progression free survival (PFS) in participants with multiple myeloma who have relapsed after 1 to 3 prior therapies.

Description:

This is a phase 3 multicenter, open-label, randomized study in participants with relapsed or refractory multiple myeloma (RRMM) who have received 1 to 3 prior therapies. Participants receive the treatment determined by randomization for a maximum of approximately 5 years, up to 30 days prior to the final analysis data cutoff (DCO) date or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or death (whichever occurs first). No crossover between the treatment arms is allowed. This was an open-label study. However, the assessment of response and disease progression for the primary analysis was determined by an Independent Review Committee (IRC) in a blinded manner. Sensitivity analyses of response and disease progression were determined centrally by the sponsor using a validated computer algorithm (Onyx Response Computational Assessment [ORCA]) in a blinded manner. Following progression or discontinuation of study drug(s), participants will have 1 follow-up visit (30 days [+3} after last dose of all study drug[s]). After disease progression, data on survival status and subsequent antimyeloma therapy will be gathered at long-term follow-up (LTFU) visits every 12 weeks (+/-2 weeks) until the Final Analysis DCO.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 466
• Est. completion date: April 15, 2022
• Est. primary completion date: July 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Criteria 1 Relapsed or progressive multiple myeloma after last treatment
• Criteria 2 Males or females = 18 years of age
• Criteria 3 Measurable disease with at least 1 of the following assessed within 21 days

prior to randomization:

• IgG multiple myeloma: serum monoclonal paraprotein (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/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
• Criteria 4 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
• Criteria 5 Prior therapy with carfilzomib is allowed as long as the patient had at least a partial response (PR) to most recent therapy with carfilzomib, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and will have at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not proteasome inhibitors or CD38 antibodies during this 6-month carfilzomib treatment free interval)
• Criteria 6 Prior therapy with anti-CD38 antibodies is allowed as long as the patient had at least a PR to most recent therapy with CD38 antibody, was not removed due to toxicity, did not relapse within 60 days from intensive treatment (at least every other week) of CD38 antibody therapy, and will have at least a 6 month CD38 antibody treatment-free interval from last dose received until first study treatment
• Other inclusion criteria may apply

Exclusion Criteria:

• Criteria 1 Waldenström macroglobulinemia
• Criteria 2 Multiple myeloma of IgM subtype
• Criteria 3 POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Criteria 4 Plasma cell leukemia (> 2.0 * 10^9/L circulating plasma cells by standard differential)
• Criteria 5 Myelodysplastic syndrome
• Criteria 6 Known moderate or severe persistent asthma within the past 2 years
• Criteria 7 Known chronic obstructive pulmonary disease (COPD) with a FEV1 < 50% of predicted normal
• Criteria 8 Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization
• Other exclusion criteria may apply

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Relapsed Multiple Myeloma

Intervention

Drug:
• Dexamethasone
Commercially available oral and IV formulas were obtained by investigative sites. Amgen supplied IV or PO dexa for some countries (Poland, Hungry, Romania, Bulgaria, Korea). Dosage modification rules applied based on participant age (participants > 75 years were given lower doses), dexa-related toxicities, and discontinuation of carfilzomib.
• Daratumumab
Daratumumab was supplied as a concentrated solution for infusion in single-use vials.
• Carfilzomib
Carfilzomib for infusion was supplied as a lyophilized, sterile product in single-use vials. The lyophilized product was reconstituted with preservative-free sterile water for injection, the reconstituted solution contained carfilzomib 2 mg/mL. IV injections lasted approximately 30 minutes. Dose could be modified based on a >20% change in body weight or toxicity.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Epworth Healthcare	East Melbourne	Victoria
Australia	St Vincents Hospital Melbourne	Fitzroy, VIC	Victoria
Australia	Barwon Health, University Hospital Geelong	Geelong	Victoria
Australia	Royal Brisbane and Womens Hospital	Herston	Queensland
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	St Vincents Hospital Sydney	St Leonards	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Medizinische Universitaet Graz	Graz
Austria	Landeskrankenhaus Salzburg	Salzburg
Belgium	Ziekenhuis Netwerk Antwerpen Stuivenberg	Antwerpen
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	Grand Hôpital de Charleroi	Charleroi
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Hematology Diseases EAD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD	Sofia
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava	Ostrava-Poruba
Czechia	Fakultni nemocnice Plzen	Plzen
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	Centre Hospitalier Départemental les Oudairies	La Roche Sur Yon Cedex 9
France	Centre Hospitalier de Versailles - Hopital Andre Mignot	Le Chesnay cedex
France	Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez	Lille Cedex
France	Centre Hospitalier Universitaire de Nantes	Nantes Cedex 1
France	Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque	Pessac Cedex
France	Centre Hospitalier Lyon Sud	Pierre-Benite cedex
France	Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie	Poitiers Cedex
France	Centre Hospitalier Universitaire de Nancy - Hopital de Brabois	Vandoeuvre les Nancy Cedex
Greece	Alexandra Hospital	Athens
Greece	General Hospital Evangelismos	Athens
Greece	General University Hospital of Patras Panagia i Voithia	Patra
Greece	Theagenion Cancer Hospital of Thessaloniki	Thessaloniki
Hungary	Bekes Megyei Kozponti Korhaz Dr Rethy Pal Tagkorhaz	Bekescsaba
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar	Szeged
Japan	Kyushu University Hospital	Fukuoka-shi	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka
Japan	Tesshokai Kameda General Hospital	Kamogawa-shi	Chiba
Japan	Saitama Medical Center	Kawagoe-shi	Saitama
Japan	Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Tokyo
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto-shi	Kyoto
Japan	Gunma University Hospital	Maebashi-shi	Gunma
Japan	Nagoya City University Hospital	Nagoya-shi	Aichi
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata
Japan	Ogaki Municipal Hospital	Ogaki-shi	Gifu
Japan	National Hospital Organization Okayama Medical Center	Okayama-shi	Okayama
Japan	National Hospital Organization Shibukawa Medical Center	Shibukawa-shi	Gunma
Japan	Japanese Red Cross Medical Center	Shibuya-ku	Tokyo
Japan	Osaka University Hospital	Suita-shi	Osaka
Japan	Tokushima Prefectural Central Hospital	Tokushima-shi	Tokushima
Japan	Toyohashi Municipal Hospital	Toyohashi-shi	Aichi
Japan	Tochigi Cancer Center	Utsunomiya-shi	Tochigi
Korea, Republic of	National Cancer Center	Goyang-si, Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun, Jeollanam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St Marys Hospital	Seoul
Poland	InterHem	Bialystok
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich w Chorzowie	Chorzow
Poland	Centrum Onkologii Ziemi Lubelskiej im Swietego Jana z Dukli	Lublin
Poland	Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K Marcinkowskiego w Poznaniu	Poznan
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Romania	Policlinica de Diagnostic Rapid	Brasov
Romania	Coltea Clinical Hospital	Bucharest
Romania	Fundeni Clinical Institute	Bucharest
Romania	Bucharest Emergency University Hospital	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Romania	Profesor Dr Ion Chiricuta Institut of Oncology	Cluj-Napoca
Romania	Spitalul Clinic Municipal Filantropia Craiova	Craiova
Russian Federation	SBHI of Nizhny Novgorod region Regional Clinical Hospital of Nizhny Novgorod na N A Semashko	Nizhny Novgorod
Russian Federation	SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov	Petrozavodsk
Russian Federation	State Budget Educational Institution of High Professional Skills Samara State Medical University	Samara
Russian Federation	Clinic of professional pathology and hematology	Saratov
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Cataluña
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Clinico Universitario de Salamanca	Salamanca	Castilla León
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Turkey	Ankara Universitesi Tip Fakultesi Cebeci Hastanesi	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara
Turkey	Ege University Faculty of Medicine	Izmir
Turkey	Ondokuz Mayis Universitesi Tip Fakultesi	Samsun
United Kingdom	St James University Hospital	Leeds
United Kingdom	University College London Hospital	London
United Kingdom	Christie Hospital	Manchester
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Lynn Cancer Center Boca Raton Regional Hospital, Lynn Cancer Institute	Boca Raton	Florida
United States	Charleston Oncology	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Chicago Medical Center - Multiple Myeloma Research Consortium	Chicago	Illinois
United States	Baylor Charles A Sammons Cancer Center at Dallas	Dallas	Texas
United States	Gabrail Cancer Center, LLC	Dover	Ohio
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Hattiesburg Clinic Hematology/Oncology	Hattiesburg	Mississippi
United States	New York Presbyterian Hospital, Weill Cornell Medical College	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  France,  Greece,  Hungary,  Japan,  Korea, Republic of,  Poland,  Romania,  Russian Federation,  Spain,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (8)

Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Yang H, Klippel Z, Zahlten-Kumeli A, Usmani SZ. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020 Jul 18;396(10245):186-197. doi: 10.1016/S0140-6736(20)30734-0. Erratum In: Lancet. 2020 Aug 15;396(10249):466. — View Citation

Landgren O, Weisel K, Rosinol L, Touzeau C, Turgut M, Hajek R, Mollee P, Kim JS, Shu N, Hu X, Li C, Usmani SZ. Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the CANDOR study. Br J Haematol. 2022 Sep;198(6):988-993. doi: 10.1111/bjh.18233. Epub 2022 May 24. — View Citation

Leleu X, Beksac M, Chou T, Dimopoulos M, Yoon SS, Prince HM, Pour L, Shelekhova T, Chari A, Khurana M, Zhang J, Obreja M, Qi M, Oriol A, Siegel D. Efficacy and safety of weekly carfilzomib (70 mg/m2), dexamethasone, and daratumumab (KdD70) is comparable to twice-weekly KdD56 while being a more convenient dosing option: a cross-study comparison of the CANDOR and EQUULEUS studies. Leuk Lymphoma. 2021 Feb;62(2):358-367. doi: 10.1080/10428194.2020.1832672. Epub 2020 Oct 28. — View Citation

Quach H, Nooka A, Samoylova O, Venner CP, Kim K, Facon T, Spencer A, Usmani SZ, Grosicki S, Suzuki K, Delimpasi S, Weisel K, Obreja M, Zahlten-Kumeli A, Mateos MV. Carfilzomib, dexamethasone and daratumumab in relapsed or refractory multiple myeloma: results of the phase III study CANDOR by prior lines of therapy. Br J Haematol. 2021 Aug;194(4):784-788. doi: 10.1111/bjh.17541. Epub 2021 May 28. No abstract available. — View Citation

Siegel D, Weisel K, Zahlten-Kumeli A, Medhekar R, Ding B, Leleu X. Health-related quality of life outcomes from the CANDOR study in patients with relapsed or refractory multiple myeloma. Leuk Lymphoma. 2021 Dec;62(12):3002-3010. doi: 10.1080/10428194.2021.1941927. Epub 2021 Jun 26. — View Citation

Suzuki K, Min CK, Kim K, Lee JJ, Shibayama H, Ko PS, Huang SY, Li SS, Ding B, Khurana M, Iida S. Carfilzomib, dexamethasone, and daratumumab in Asian patients with relapsed or refractory multiple myeloma: post hoc subgroup analysis of the phase 3 CANDOR trial. Int J Hematol. 2021 Dec;114(6):653-663. doi: 10.1007/s12185-021-03204-9. Epub 2021 Aug 19. — View Citation

Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Gavriatopoulou M, Oriol A, Rabin N, Nooka A, Qi M, Beksac M, Jakubowiak A, Ding B, Zahlten-Kumeli A, Yusuf A, Dimopoulos M. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022 Jan;23(1):65-76. doi: 10.1016/S1470-2045(21)00579-9. Epub 2021 Dec 3. — View Citation

Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Shu X, Li C, Dimopoulos M. Final analysis of carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone in the CANDOR study. Blood Adv. 2023 Jul 25;7(14):3739-3748. doi: 10.1182/bloodadvances.2023010026. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) as Assessed by the Independent Review Committee (PA DCO Only)	Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Participants were evaluated for disease response and progression according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) as assessed by an Independent Review Committee (IRC). The duration of PFS was right censored for participants who met any of the following conditions: 1. no baseline/post-baseline disease assessments; 2. started a new anti myeloma therapy before documentation of progressive disease or death; 3. progressive disease or death immediately after more than 70 days without disease assessment visit or; 4. alive without documentation of disease progression before the analysis trigger date (PA DCO); 5. lost to follow-up or withdrawn consent.	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary	Overall Response (OR) as Assessed by the Independent Review Committee (PA DCO Only)	Overall response rate was defined as the percentage of participants in each treatment group who achieve partial response (PR) or better per the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) as their best response.; Complete Response (CR): No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.; Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation but not electrophoresis or = 90% reduction in serum M-component with urine M-component <100 mg/24 hours.; Partial Response (PR): = 50% reduction of serum M-protein and reduction in urine M-protein by = 90% or to < 200 mg/24 hours. A = 50% reduction in the size of soft tissue plasmacytomas if present at baseline.; 95% CIs for proportions were estimated using the Clopper-Pearson method.	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary	Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee	MRD[-]CR at 12 months was defined as achievement of CR per IMWG-URC by IRC and MRD[-] status as assessed by next-generation sequencing (NGS; at a 10^-5 level) at the 12 months landmark (8 to 13 month window).	12 Months (8- to 13-month window)
Secondary	Overall Survival	Overall survival was defined as the time from randomization until death from any cause. Deaths collected via public source, after end of study were included. Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. Participants still alive were censored at the date last known to be alive.	Up to 58 months after the first participant was enrolled (at FA DCO, a median of 40.29 weeks of treatment [any study drug] in the Kd group and 79.29 weeks of treatment [any study drug] in the KdD group; FA DCO was 15 Apr 2022)
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Treatment-emergent adverse events are defined as any adverse event with an onset after the administration of the first dose of any study treatment and within the end of study or 30 days of the last dose of any study treatment, whichever occurs earlier.; The severity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal.; Treatment-related adverse events are treatment-emergent adverse events considered related to at least one study drug by the investigator, including those with unknown relationship.	PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks
Secondary	Kaplan-Meier Estimate for Duration of Response (DOR) (PA DCO Only)	Duration of response (DOR) was defined as the time (in months) from first evidence of partial response (PR) or better per IMWG-URC by IRC to the earlier of disease progression or death due to any cause for participants with a best response of PR or better. For those who are alive and have not experienced disease progression at the time of data cutoff for analysis, duration of response was right-censored.; Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.	From Day 1 until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary	Kaplan-Meier Estimate for Time to Next Treatment (TTNT)	Time to next treatment was defined as the time (in months) from randomization to the initiation of subsequent non-protocol anti-cancer treatment for multiple myeloma. Time to next treatment for participants who do not start the subsequent treatment for multiple myeloma was censored at the date when the participant's information was last available.; Medians of TTNT duration were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.	PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks
Secondary	Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (PA DCO Only)	Time to progression was defined as the time (in months) from randomization to documented disease progression. Participants who did not have documented disease progression were censored at the date when data was last available.	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary	Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only)	Time to progression was defined as the time (in months) from randomization to documented disease progression. This outcome reports TTP as the percentage of participants who were event free (that is, they had not had disease progression) at the specified time frames. Independent Review Committee assessment for this outcome measure was not planned after the primary analysis.; 95% CIs for event-free rates were estimated using the method by Kalbfleisch and Prentice (1980) with log-log transformation.	Randomization to Months 3, 6, 12, and 18
Secondary	Time to Overall Response as Assessed by the Independent Review Committee (PA DCO Only)	Time to overall response was defined as the time from randomization to the earliest date a response of partial response (PR) or better as per IMWG-URC is first achieved and subsequently confirmed for participants with a best response of PR or better.	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary	Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More	A measure of the persistence of the CR (includes strict CR) per International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and MRD[-] status as assessed by next-generation sequencing (NGS; at a 10^-5 level) for 12 months or more after achieving MRD[-]CR status.; 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.	PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks
Secondary	Percentage of Participants With a Complete Response (CR) as Assessed by the Independent Review Committee (PA DCO Only)	The percentage of participants in each treatment group who achieved stringent complete response (sCR) or CR per IMWG-URC, as assessed by the IRC, as their best response is presented.	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary	Percentage of Participants Who Achieved Minimal Residual Disease Negative (MRD[-]) Status as Assessed by Next Generation Sequencing at 12 Months	MRD[-] at 12-month was defined as achievement of MRD[-] status as assessed by next-generation sequencing (NGS; at a 10^-5 level) at the 12 months landmark (from 8 months to 13 months window).; 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.	12 Months (8- to 13-month window)
Secondary	Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose	Health-related quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer Quality of Life Core Module (QLQ-C30) questionnaire, a validated instrument in multiple myeloma patients. Scores range from 0 to 100, with higher scores indicating better health related quality of life.; QLQ-C30 questionnaire was administered prior to dosing every 28 ± 7 days starting from cycle 1 day 1 through first follow-up visit (30 days [+3] after last dose of all study drugs).	Baseline (Day 1 pre-dose) up to 236.3 weeks (longest treatment duration as of the FA DCO)

External Links

•   AmgenTrials clinical trials website