Study 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.

Condition or Disease	Intervention/Treatment
Relapsed Multiple Myeloma Refractory Multiple Myeloma	Drug: Dexamethasone Drug: Daratumumab Drug: Carfilzomib

Study Design

Study Type	Interventional
Actual Enrollment	466 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
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
Study Start Date	June 13, 2017
Actual Primary Completion Date	July 14, 2019
Actual Study Completion Date	April 15, 2022

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Kd - Carfilzomib and Dexamethasone Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	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. Drug: Carfilzomib
KdD - Carfilzomib, Dexamethasone and Daratumumab Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg was further continued on Cycles 7+: day 1 only.	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. Drug: Daratumumab Drug: Carfilzomib

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) as Assessed by the Independent Review Committee (PA DCO Only) [From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks]
   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.

Secondary Outcome Measures

1. Overall Response (OR) as Assessed by the Independent Review Committee (PA DCO Only) [From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks]
   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.
2. Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee [12 Months (8- to 13-month window)]
   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).
3. Overall Survival [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)]
   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.
4. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [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]
   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.
5. Kaplan-Meier Estimate for Duration of Response (DOR) (PA DCO Only) [From Day 1 until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks]
   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.
6. Kaplan-Meier Estimate for Time to Next Treatment (TTNT) [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]
   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.
7. Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (PA DCO Only) [From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks]
   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.
8. 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) [Randomization to Months 3, 6, 12, and 18]
   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.
9. Time to Overall Response as Assessed by the Independent Review Committee (PA DCO Only) [From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks]
   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.
10. Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More [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]
    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.
11. Percentage of Participants With a Complete Response (CR) as Assessed by the Independent Review Committee (PA DCO Only) [From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks]
    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.
12. Percentage of Participants Who Achieved Minimal Residual Disease Negative (MRD[-]) Status as Assessed by Next Generation Sequencing at 12 Months [12 Months (8- to 13-month window)]
    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.
13. 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 [Baseline (Day 1 pre-dose) up to 236.3 weeks (longest treatment duration as of the FA DCO)]
    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).

Eligibility Criteria

Ages Eligible for Study	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
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

Contacts and Locations

Sponsors and Collaborators	Amgen
Locations	Lynn Cancer Center Boca Raton Regional Hospital, Lynn Cancer Institute | Boca Raton, Florida, United States, 33486 Emory University Winship Cancer Institute | Atlanta, Georgia, United States, 30322 University of Chicago Medical Center - Multiple Myeloma Research Consortium | Chicago, Illinois, United States, 60637-6613 Fort Wayne Medical Oncology and Hematology | Fort Wayne, Indiana, United States, 46845 Hattiesburg Clinic Hematology/Oncology | Hattiesburg, Mississippi, United States, 39401 Hackensack University Medical Center | Hackensack, New Jersey, United States, 07601 New York Presbyterian Hospital, Weill Cornell Medical College | New York, New York, United States, 10021 Levine Cancer Institute | Charlotte, North Carolina, United States, 28204 Gabrail Cancer Center, LLC | Dover, Ohio, United States, 44622 Charleston Oncology | Charleston, South Carolina, United States, 29414 Baylor Charles A Sammons Cancer Center at Dallas | Dallas, Texas, United States, 75246 Liverpool Hospital | Liverpool, New South Wales, Australia, 2170 St Vincents Hospital Sydney | St Leonards, New South Wales, Australia, 2065 Westmead Hospital | Westmead, New South Wales, Australia, 2145 Royal Brisbane and Womens Hospital | Herston, Queensland, Australia, 4029 Princess Alexandra Hospital | Woolloongabba, Queensland, Australia, 4102 Royal Adelaide Hospital | Adelaide, South Australia, Australia, 5000 Epworth Healthcare | East Melbourne, Victoria, Australia, 3002 St Vincents Hospital Melbourne | Fitzroy, VIC, Victoria, Australia, 3065 Barwon Health, University Hospital Geelong | Geelong, Victoria, Australia, 3220 The Alfred Hospital | Melbourne, Victoria, Australia, 3004 Medizinische Universitaet Graz | Graz, Austria, 8036 Landeskrankenhaus Salzburg | Salzburg, Austria, 5020 Ziekenhuis Netwerk Antwerpen Stuivenberg | Antwerpen, Belgium, 2060 Universitair Ziekenhuis Brussel | Brussel, Belgium, 1090 Grand Hôpital de Charleroi | Charleroi, Belgium, 6000 Universitair Ziekenhuis Gent | Gent, Belgium, 9000 Universitair Ziekenhuis Leuven - Campus Gasthuisberg | Leuven, Belgium, 3000 University Multiprofile Hospital for Active Treatment Sveti Georgi EAD | Plovdiv, Bulgaria, 4002 University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD | Sofia, Bulgaria, 1431 Specialized Hospital for Active Treatment of Hematology Diseases EAD | Sofia, Bulgaria, 1756 Tom Baker Cancer Centre | Calgary, Alberta, Canada, T2N 4N2 Cross Cancer Institute | Edmonton, Alberta, Canada, T6G 1Z2 Ottawa Hospital Research Institute | Ottawa, Ontario, Canada, K1H 8L6 Princess Margaret Cancer Centre | Toronto, Ontario, Canada, M5G 2M9 Hopital Maisonneuve-Rosemont | Montreal, Quebec, Canada, H1T 2M4 Fakultni nemocnice Brno | Brno, Czechia, 625 00 Fakultni nemocnice Hradec Kralove | Hradec Kralove, Czechia, 500 05 Fakultni nemocnice Ostrava | Ostrava-Poruba, Czechia, 708 52 Fakultni nemocnice Plzen | Plzen, Czechia, 304 60 Vseobecna fakultni nemocnice v Praze | Praha 2, Czechia, 128 08 Centre Hospitalier Départemental les Oudairies | La Roche Sur Yon Cedex 9, France, 85925 Centre Hospitalier de Versailles - Hopital Andre Mignot | Le Chesnay cedex, France, 78157 Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez | Lille Cedex, France, 59037 Centre Hospitalier Universitaire de Nantes | Nantes Cedex 1, France, 44093 Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque | Pessac Cedex, France, 33604 Centre Hospitalier Lyon Sud | Pierre-Benite cedex, France, 69495 Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie | Poitiers Cedex, France, 86021 Centre Hospitalier Universitaire de Nancy - Hopital de Brabois | Vandoeuvre les Nancy Cedex, France, 54511 General Hospital Evangelismos | Athens, Greece, 10676 Alexandra Hospital | Athens, Greece, 11528 General University Hospital of Patras Panagia i Voithia | Patra, Greece, 26504 Theagenion Cancer Hospital of Thessaloniki | Thessaloniki, Greece, 54007 Bekes Megyei Kozponti Korhaz Dr Rethy Pal Tagkorhaz | Bekescsaba, Hungary, 5600 Semmelweis Egyetem | Budapest, Hungary, 1088 Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet | Budapest, Hungary, 1097 Debreceni Egyetem Klinikai Kozpont | Debrecen, Hungary, 4032 Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar | Szeged, Hungary, 6725 Nagoya City University Hospital | Nagoya-shi, Aichi, Japan, 467-8602 Toyohashi Municipal Hospital | Toyohashi-shi, Aichi, Japan, 441-8570 Tesshokai Kameda General Hospital | Kamogawa-shi, Chiba, Japan, 296-8602 National Hospital Organization Kyushu Cancer Center | Fukuoka-shi, Fukuoka, Japan, 811-1395 Kyushu University Hospital | Fukuoka-shi, Fukuoka, Japan, 812-8582 Ogaki Municipal Hospital | Ogaki-shi, Gifu, Japan, 503-8502 Gunma University Hospital | Maebashi-shi, Gunma, Japan, 371-8511 National Hospital Organization Shibukawa Medical Center | Shibukawa-shi, Gunma, Japan, 377-0280 University Hospital Kyoto Prefectural University of Medicine | Kyoto-shi, Kyoto, Japan, 602-8566 Niigata Cancer Center Hospital | Niigata-shi, Niigata, Japan, 951-8566 National Hospital Organization Okayama Medical Center | Okayama-shi, Okayama, Japan, 701-1192 Osaka University Hospital | Suita-shi, Osaka, Japan, 565-0871 Saitama Medical Center | Kawagoe-shi, Saitama, Japan, 350-8550 Tochigi Cancer Center | Utsunomiya-shi, Tochigi, Japan, 320-0834 Tokushima Prefectural Central Hospital | Tokushima-shi, Tokushima, Japan, 770-8539 Cancer Institute Hospital of Japanese Foundation for Cancer Research | Koto-ku, Tokyo, Japan, 135-8550 Japanese Red Cross Medical Center | Shibuya-ku, Tokyo, Japan, 150-8935 National Cancer Center | Goyang-si, Gyeonggi-do, Korea, Republic of, 10408 Chonnam National University Hwasun Hospital | Hwasun, Jeollanam-do, Korea, Republic of, 58128 Seoul National University Hospital | Seoul, Korea, Republic of, 03080 Severance Hospital Yonsei University Health System | Seoul, Korea, Republic of, 03722 Asan Medical Center | Seoul, Korea, Republic of, 05505 Samsung Medical Center | Seoul, Korea, Republic of, 06351 The Catholic University of Korea Seoul St Marys Hospital | Seoul, Korea, Republic of, 06591 InterHem | Bialystok, Poland, 15-732 Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich w Chorzowie | Chorzow, Poland, 41-500 Centrum Onkologii Ziemi Lubelskiej im Swietego Jana z Dukli | Lublin, Poland, 20-090 Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K Marcinkowskiego w Poznaniu | Poznan, Poland, 60-569 Instytut Hematologii i Transfuzjologii | Warszawa, Poland, 02-776 Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu | Wroclaw, Poland, 50-367 Policlinica de Diagnostic Rapid | Brasov, Romania, 500152 Fundeni Clinical Institute | Bucharest, Romania, 022328 Coltea Clinical Hospital | Bucharest, Romania, 030171 Spitalul Clinic Colentina | Bucuresti, Romania, 020125 Bucharest Emergency University Hospital | Bucuresti, Romania, 050098 Profesor Dr Ion Chiricuta Institut of Oncology | Cluj-Napoca, Romania, 400124 Spitalul Clinic Municipal Filantropia Craiova | Craiova, Romania, 200143 SBHI of Nizhny Novgorod region Regional Clinical Hospital of Nizhny Novgorod na N A Semashko | Nizhny Novgorod, Russian Federation, 603126 SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov | Petrozavodsk, Russian Federation, 185019 State Budget Educational Institution of High Professional Skills Samara State Medical University | Samara, Russian Federation, 443079 Clinic of professional pathology and hematology | Saratov, Russian Federation, 410028 Hospital Clinico Universitario de Salamanca | Salamanca, Castilla León, Spain, 37007 Hospital Universitari Germans Trias i Pujol | Badalona, Cataluña, Spain, 08916 Hospital Clinic i Provincial de Barcelona | Barcelona, Cataluña, Spain, 08036 Clinica Universidad de Navarra | Pamplona, Navarra, Spain, 31008 Hospital Universitario 12 de Octubre | Madrid, Spain, 28041 National Taiwan University Hospital | Taipei, Taiwan, 10002 Taipei Veterans General Hospital | Taipei, Taiwan, 11217 Hacettepe Universitesi Tip Fakultesi | Ankara, Turkey, 06100 Ankara Universitesi Tip Fakultesi Cebeci Hastanesi | Ankara, Turkey, 06590 Ege University Faculty of Medicine | Izmir, Turkey, 35040 Ondokuz Mayis Universitesi Tip Fakultesi | Samsun, Turkey, 55139 St James University Hospital | Leeds, United Kingdom, LS9 7TF University College London Hospital | London, United Kingdom, NW1 2PG Christie Hospital | Manchester, United Kingdom, M20 4BX
Investigators

Study Documents (Full Text)

• Documents Provided by Amgen: Study Protocol March 17, 2021
• Documents Provided by Amgen: Statistical Analysis Plan July 15, 2019

More Information

Additional Information

• AmgenTrials clinical trials website

Publications

• 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.

• 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.

• 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.

• 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.

• 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.

• 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. doi: 10.1016/S0140-6736(20)31669-X.

• 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.

• 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.

Additional Relevant MeSH Terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Neoplasms by Histologic Type
• Neoplasms
• Hemostatic Disorders
• Vascular Diseases
• Cardiovascular Diseases
• Paraproteinemias
• Blood Protein Disorders
• Hematologic Diseases
• Hemorrhagic Disorders
• Lymphoproliferative Disorders
• Immunoproliferative Disorders
• Immune System Diseases