CANDOR: Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma.
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT03158688
Collaborator
(none)
466
113
2
58.1
4.1
0.1
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed 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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
466 participants
Allocation:
Randomized
Intervention 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
Actual Study Start Date
:
Jun 13, 2017
Actual Primary Completion Date
:
Jul 14, 2019
Actual Study Completion Date
:
Apr 15, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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
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.
Other Names:
|
| Experimental: 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
Daratumumab was supplied as a concentrated solution for infusion in single-use vials.
Other Names:
Drug: 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) [From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group.]
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).
Secondary Outcome Measures
- Overall Response (OR) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) [From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group.]
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.
- Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) [12 Months (8- to 13-month window)]
MRD[-]CR at 12 months was defined as achievement of CR per International Myeloma Working Group-Uniform Response Criteria and MRD[-] status as assessed by next-generation sequencing (NGS) at the 12 months landmark (8 to 13 month window).
- Overall Survival [At approximately 230 OS events or 58 months after the first participant is enrolled, whichever occurs earlier.]
Overall survival was defined as the time from randomization until death from any cause.
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Data Cut-off Date 14 July 2019) [From Day 1 until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group.]
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 where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal. Treatment-related adverse events are adverse events considered related to at least one investigational product by the investigator, including those with unknown relationship.
- Kaplan-Meier Estimate for Duration of Response (DOR) (Data Cut-off Date 14 July 2019) [Day 1 until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group.]
Duration of response (DOR) was defined as the time (in months) from first evidence of partial response (PR) or better per IMWG-URC 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.
- Kaplan-Meier Estimate for Time to Next Treatment (TTNT) (Data Cut-off Date 14 July 2019) [From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group.]
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.
- Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) [From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group]
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.
- 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 (Data Cut-off Date 14 July 2019) [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.
- Time to Overall Response as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) [From randomization until the data cut-off date of 14 July 2019; the maximum time to response was 14 months]
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.
- Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More (Data Cut-off Date 14 July 2019) [Month 8 to 25 months (maximum time as of data cut-off)]
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) for 12 months or more after achieving MRD[-]CR status. 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.
- Time to Complete Response (CR) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) [From randomization until the data cut-off date of 14 July 2019; the maximum time to CR was 16 months.]
Time to complete response was defined as the time from randomization to the earliest date a response of strict complete response (sCR) or complete response (CR) per IMWG-URC is first achieved and subsequently confirmed.
- 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 the 12 months landmark (from 8 months to 13 months window). 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.
- 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 (Data Cut-off Date 14 July 2019) [Baseline (Day 1 pre-dose) up to Week 102 (maximum treatment by cut-off)]
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). (data cut-off date 14 July 2019)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lynn Cancer Center Boca Raton Regional Hospital, Lynn Cancer Institute | Boca Raton | Florida | United States | 33486 |
| 2 | Emory University Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 3 | University of Chicago Medical Center - Multiple Myeloma Research Consortium | Chicago | Illinois | United States | 60637-6613 |
| 4 | Fort Wayne Medical Oncology and Hematology | Fort Wayne | Indiana | United States | 46845 |
| 5 | Hattiesburg Clinic Hematology/Oncology | Hattiesburg | Mississippi | United States | 39401 |
| 6 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 7 | New York Presbyterian Hospital, Weill Cornell Medical College | New York | New York | United States | 10021 |
| 8 | Levine Cancer Institute | Charlotte | North Carolina | United States | 28204 |
| 9 | Gabrail Cancer Center, LLC | Dover | Ohio | United States | 44622 |
| 10 | Charleston Oncology | Charleston | South Carolina | United States | 29414 |
| 11 | Baylor Charles A Sammons Cancer Center at Dallas | Dallas | Texas | United States | 75246 |
| 12 | Liverpool Hospital | Liverpool | New South Wales | Australia | 2170 |
| 13 | St Vincents Hospital Sydney | St Leonards | New South Wales | Australia | 2065 |
| 14 | Westmead Hospital | Westmead | New South Wales | Australia | 2145 |
| 15 | Royal Brisbane and Womens Hospital | Herston | Queensland | Australia | 4029 |
| 16 | Princess Alexandra Hospital | Woolloongabba | Queensland | Australia | 4102 |
| 17 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | 5000 |
| 18 | Epworth Healthcare | East Melbourne | Victoria | Australia | 3002 |
| 19 | St Vincents Hospital Melbourne | Fitzroy, VIC | Victoria | Australia | 3065 |
| 20 | Barwon Health, University Hospital Geelong | Geelong | Victoria | Australia | 3220 |
| 21 | The Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
| 22 | Medizinische Universitaet Graz | Graz | Austria | 8036 | |
| 23 | Landeskrankenhaus Salzburg | Salzburg | Austria | 5020 | |
| 24 | Ziekenhuis Netwerk Antwerpen Stuivenberg | Antwerpen | Belgium | 2060 | |
| 25 | Universitair Ziekenhuis Brussel | Brussel | Belgium | 1090 | |
| 26 | Grand Hôpital de Charleroi | Charleroi | Belgium | 6000 | |
| 27 | Universitair Ziekenhuis Gent | Gent | Belgium | 9000 | |
| 28 | Universitair Ziekenhuis Leuven - Campus Gasthuisberg | Leuven | Belgium | 3000 | |
| 29 | University Multiprofile Hospital for Active Treatment Sveti Georgi EAD | Plovdiv | Bulgaria | 4002 | |
| 30 | University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD | Sofia | Bulgaria | 1431 | |
| 31 | Specialized Hospital for Active Treatment of Hematology Diseases EAD | Sofia | Bulgaria | 1756 | |
| 32 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4N2 |
| 33 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
| 34 | Ottawa Hospital Research Institute | Ottawa | Ontario | Canada | K1H 8L6 |
| 35 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 2M9 |
| 36 | Hopital Maisonneuve-Rosemont | Montreal | Quebec | Canada | H1T 2M4 |
| 37 | Fakultni nemocnice Brno | Brno | Czechia | 625 00 | |
| 38 | Fakultni nemocnice Hradec Kralove | Hradec Kralove | Czechia | 500 05 | |
| 39 | Fakultni nemocnice Ostrava | Ostrava-Poruba | Czechia | 708 52 | |
| 40 | Fakultni nemocnice Plzen | Plzen | Czechia | 304 60 | |
| 41 | Vseobecna fakultni nemocnice v Praze | Praha 2 | Czechia | 128 08 | |
| 42 | Centre Hospitalier Départemental les Oudairies | La Roche Sur Yon Cedex 9 | France | 85925 | |
| 43 | Centre Hospitalier de Versailles - Hopital Andre Mignot | Le Chesnay cedex | France | 78157 | |
| 44 | Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez | Lille Cedex | France | 59037 | |
| 45 | Centre Hospitalier Universitaire de Nantes | Nantes Cedex 1 | France | 44093 | |
| 46 | Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque | Pessac Cedex | France | 33604 | |
| 47 | Centre Hospitalier Lyon Sud | Pierre-Benite cedex | France | 69495 | |
| 48 | Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie | Poitiers Cedex | France | 86021 | |
| 49 | Centre Hospitalier Universitaire de Nancy - Hopital de Brabois | Vandoeuvre les Nancy Cedex | France | 54511 | |
| 50 | General Hospital Evangelismos | Athens | Greece | 10676 | |
| 51 | Alexandra Hospital | Athens | Greece | 11528 | |
| 52 | General University Hospital of Patras Panagia i Voithia | Patra | Greece | 26504 | |
| 53 | Theagenion Cancer Hospital of Thessaloniki | Thessaloniki | Greece | 54007 | |
| 54 | Bekes Megyei Kozponti Korhaz Dr Rethy Pal Tagkorhaz | Bekescsaba | Hungary | 5600 | |
| 55 | Semmelweis Egyetem | Budapest | Hungary | 1088 | |
| 56 | Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet | Budapest | Hungary | 1097 | |
| 57 | Debreceni Egyetem Klinikai Kozpont | Debrecen | Hungary | 4032 | |
| 58 | Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar | Szeged | Hungary | 6725 | |
| 59 | Nagoya City University Hospital | Nagoya-shi | Aichi | Japan | 467-8602 |
| 60 | Toyohashi Municipal Hospital | Toyohashi-shi | Aichi | Japan | 441-8570 |
| 61 | Tesshokai Kameda General Hospital | Kamogawa-shi | Chiba | Japan | 296-8602 |
| 62 | National Hospital Organization Kyushu Cancer Center | Fukuoka-shi | Fukuoka | Japan | 811-1395 |
| 63 | Kyushu University Hospital | Fukuoka-shi | Fukuoka | Japan | 812-8582 |
| 64 | Ogaki Municipal Hospital | Ogaki-shi | Gifu | Japan | 503-8502 |
| 65 | Gunma University Hospital | Maebashi-shi | Gunma | Japan | 371-8511 |
| 66 | National Hospital Organization Shibukawa Medical Center | Shibukawa-shi | Gunma | Japan | 377-0280 |
| 67 | University Hospital Kyoto Prefectural University of Medicine | Kyoto-shi | Kyoto | Japan | 602-8566 |
| 68 | Niigata Cancer Center Hospital | Niigata-shi | Niigata | Japan | 951-8566 |
| 69 | National Hospital Organization Okayama Medical Center | Okayama-shi | Okayama | Japan | 701-1192 |
| 70 | Osaka University Hospital | Suita-shi | Osaka | Japan | 565-0871 |
| 71 | Saitama Medical Center | Kawagoe-shi | Saitama | Japan | 350-8550 |
| 72 | Tochigi Cancer Center | Utsunomiya-shi | Tochigi | Japan | 320-0834 |
| 73 | Tokushima Prefectural Central Hospital | Tokushima-shi | Tokushima | Japan | 770-8539 |
| 74 | Cancer Institute Hospital of Japanese Foundation for Cancer Research | Koto-ku | Tokyo | Japan | 135-8550 |
| 75 | Japanese Red Cross Medical Center | Shibuya-ku | Tokyo | Japan | 150-8935 |
| 76 | National Cancer Center | Goyang-si, Gyeonggi-do | Korea, Republic of | 10408 | |
| 77 | Chonnam National University Hwasun Hospital | Hwasun, Jeollanam-do | Korea, Republic of | 58128 | |
| 78 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 79 | Severance Hospital Yonsei University Health System | Seoul | Korea, Republic of | 03722 | |
| 80 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 81 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
| 82 | The Catholic University of Korea Seoul St Marys Hospital | Seoul | Korea, Republic of | 06591 | |
| 83 | InterHem | Bialystok | Poland | 15-732 | |
| 84 | Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich w Chorzowie | Chorzow | Poland | 41-500 | |
| 85 | Centrum Onkologii Ziemi Lubelskiej im Swietego Jana z Dukli | Lublin | Poland | 20-090 | |
| 86 | Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K Marcinkowskiego w Poznaniu | Poznan | Poland | 60-569 | |
| 87 | Instytut Hematologii i Transfuzjologii | Warszawa | Poland | 02-776 | |
| 88 | Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu | Wroclaw | Poland | 50-367 | |
| 89 | Policlinica de Diagnostic Rapid | Brasov | Romania | 500152 | |
| 90 | Fundeni Clinical Institute | Bucharest | Romania | 022328 | |
| 91 | Coltea Clinical Hospital | Bucharest | Romania | 030171 | |
| 92 | Spitalul Clinic Colentina | Bucuresti | Romania | 020125 | |
| 93 | Bucharest Emergency University Hospital | Bucuresti | Romania | 050098 | |
| 94 | Profesor Dr Ion Chiricuta Institut of Oncology | Cluj-Napoca | Romania | 400124 | |
| 95 | Spitalul Clinic Municipal Filantropia Craiova | Craiova | Romania | 200143 | |
| 96 | SBHI of Nizhny Novgorod region Regional Clinical Hospital of Nizhny Novgorod na N A Semashko | Nizhny Novgorod | Russian Federation | 603126 | |
| 97 | SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov | Petrozavodsk | Russian Federation | 185019 | |
| 98 | State Budget Educational Institution of High Professional Skills Samara State Medical University | Samara | Russian Federation | 443079 | |
| 99 | Clinic of professional pathology and hematology | Saratov | Russian Federation | 410028 | |
| 100 | Hospital Clinico Universitario de Salamanca | Salamanca | Castilla León | Spain | 37007 |
| 101 | Hospital Universitari Germans Trias i Pujol | Badalona | Cataluña | Spain | 08916 |
| 102 | Hospital Clinic i Provincial de Barcelona | Barcelona | Cataluña | Spain | 08036 |
| 103 | Clinica Universidad de Navarra | Pamplona | Navarra | Spain | 31008 |
| 104 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 105 | National Taiwan University Hospital | Taipei | Taiwan | 10002 | |
| 106 | Taipei Veterans General Hospital | Taipei | Taiwan | 11217 | |
| 107 | Hacettepe Universitesi Tip Fakultesi | Ankara | Turkey | 06100 | |
| 108 | Ankara Universitesi Tip Fakultesi Cebeci Hastanesi | Ankara | Turkey | 06590 | |
| 109 | Ege University Faculty of Medicine | Izmir | Turkey | 35040 | |
| 110 | Ondokuz Mayis Universitesi Tip Fakultesi | Samsun | Turkey | 55139 | |
| 111 | St James University Hospital | Leeds | United Kingdom | LS9 7TF | |
| 112 | University College London Hospital | London | United Kingdom | NW1 2PG | |
| 113 | Christie Hospital | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
More Information
Additional Information:
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.
- 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.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT03158688
Other Study ID Numbers:
- 20160275
- 2016-003554-33
First Posted:
May 18, 2017
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 102 centers in Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, France, Greece, Hungary, Japan, Poland, Romania, Russia, South Korea, Spain, Taiwan, Turkey, United Kingdom, and United States. 569 subjects were screened and 466 were enrolled. |
|---|---|
| Pre-assignment Detail | Participants were randomized in 1:2 ratio to arms KD vs. KdD after being stratified by 1) International Staging System (ISS) stage (Stage 1-2 vs Stage 3) at screening, 2) prior proteasome inhibitor exposure (yes/no), 3) number of prior lines of therapy (1 vs ≥ 2), and 4) prior cluster differentiation antigen 38 (CD38) antibody therapy (yes/no). |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Period Title: Overall Study | ||
| STARTED | 154 | 312 |
| Treated | 153 | 308 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 154 | 312 |
Baseline Characteristics
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. | Total of all reporting groups |
| Overall Participants | 154 | 312 | 466 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.3
(9.6)
|
62.9
(10.0)
|
63.4
(9.9)
|
| Age, Customized (Count of Participants) | |||
| 18 - 64 years |
77
50%
|
163
52.2%
|
240
51.5%
|
| 65 - 74 years |
55
35.7%
|
121
38.8%
|
176
37.8%
|
| 75 - 84 years |
22
14.3%
|
28
9%
|
50
10.7%
|
| >=85 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
63
40.9%
|
135
43.3%
|
198
42.5%
|
| Male |
91
59.1%
|
177
56.7%
|
268
57.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
0.6%
|
7
2.2%
|
8
1.7%
|
| Not Hispanic or Latino |
146
94.8%
|
291
93.3%
|
437
93.8%
|
| Unknown or Not Reported |
7
4.5%
|
14
4.5%
|
21
4.5%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Asian |
20
13%
|
46
14.7%
|
66
14.2%
|
| Black or African American |
2
1.3%
|
7
2.2%
|
9
1.9%
|
| White |
123
79.9%
|
243
77.9%
|
366
78.5%
|
| Other |
9
5.8%
|
16
5.1%
|
25
5.4%
|
| Fraility Status as Assessed by Investigator (Count of Participants) | |||
| Fit |
68
44.2%
|
176
56.4%
|
244
52.4%
|
| Intermediate fitness |
36
23.4%
|
54
17.3%
|
90
19.3%
|
| Frail |
9
5.8%
|
10
3.2%
|
19
4.1%
|
| Not available |
37
24%
|
66
21.2%
|
103
22.1%
|
| Missing |
4
2.6%
|
6
1.9%
|
10
2.1%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | |||
| Disease status 0 or 1 |
147
95.5%
|
295
94.6%
|
442
94.8%
|
| Disease status 2 |
7
4.5%
|
15
4.8%
|
22
4.7%
|
| Missing |
0
0%
|
2
0.6%
|
2
0.4%
|
| Time from Initial Diagnosis to Randomization (months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [months] |
44.03
(36.57)
|
47.86
(34.69)
|
46.58
(35.34)
|
| Risk Group as Determined by Fluorescent in situ Hybridization (FISH) (Count of Participants) | |||
| High risk |
26
16.9%
|
48
15.4%
|
74
15.9%
|
| Standard risk |
52
33.8%
|
104
33.3%
|
156
33.5%
|
| Unknlown |
76
49.4%
|
160
51.3%
|
236
50.6%
|
| Stratification Factor: International Staging System (ISS) Stage (Count of Participants) | |||
| Stage I or II |
127
82.5%
|
252
80.8%
|
379
81.3%
|
| Stage III |
27
17.5%
|
60
19.2%
|
87
18.7%
|
| Stratification Factor: Lines of Prior Treatment (Count of Participants) | |||
| 1 prior treatment |
67
43.5%
|
133
42.6%
|
200
42.9%
|
| > = 2 prior treatments |
87
56.5%
|
179
57.4%
|
266
57.1%
|
| Stratification Factor: Prior Proteasome Inhibitor Treatment (Count of Participants) | |||
| Yes |
139
90.3%
|
290
92.9%
|
429
92.1%
|
| No |
15
9.7%
|
22
7.1%
|
37
7.9%
|
| Stratification Factor: Prior CD38 Antibody Therapy (Count of Participants) | |||
| Yes |
0
0%
|
1
0.3%
|
1
0.2%
|
| No |
154
100%
|
311
99.7%
|
465
99.8%
|
| Geographic Regions (Count of Participants) | |||
| North America |
12
7.8%
|
21
6.7%
|
33
7.1%
|
| Europe |
103
66.9%
|
207
66.3%
|
310
66.5%
|
| Asia Pacific |
39
25.3%
|
84
26.9%
|
123
26.4%
|
Outcome Measures
| Title | Progression-free Survival (PFS) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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). |
| Time Frame | From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Participants with PFS events |
68
44.2%
|
110
35.3%
|
| Participants who were censored |
86
55.8%
|
202
64.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Comments | Stratification factors used in the Log-rank p-value (1-sided) and the Cox model hazard ratio (KdD/Kd) were as assessed at randomization: International Staging System stage at screening (Stage 1 or 2 vs Stage 3); prior proteasome inhibitor exposure (yes vs no); number of prior lines of therapy (1 vs >= 2). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0014 |
| Comments | alpha level of 0.025 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Stratified Cox model hazard ratio |
| Estimated Value | 0.630 | |
| Confidence Interval |
(2-Sided) 95% 0.464 to 0.854 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | KdD/Kd | |
| Title | Overall Response (OR) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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. |
| Time Frame | From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Number (95% Confidence Interval) [percentage of participants] |
74.7
48.5%
|
84.3
27%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Comments | Odds ratios and corresponding 95% CIs were estimated using the stratified Mantel-Haenszel method. P-values were calculated using the stratified Cochran-Mantel-Haenszel Chi-Square test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0040 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.925 | |
| Confidence Interval |
(2-Sided) 95% 1.184 to 3.129 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | KdD/Kd | |
| Title | Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | MRD[-]CR at 12 months was defined as achievement of CR per International Myeloma Working Group-Uniform Response Criteria and MRD[-] status as assessed by next-generation sequencing (NGS) at the 12 months landmark (8 to 13 month window). |
| Time Frame | 12 Months (8- to 13-month window) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Number (95% Confidence Interval) [percentage of participants] |
1.3
0.8%
|
12.5
4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Comments | Odds ratios and corresponding 95% CIs were estimated using the stratified Mantel-Haenszel method. 1-sided p-value from the Cochren-Mentel-Haenszel chi-squire test controlling for the randomization stratification factors. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 11.329 | |
| Confidence Interval |
(2-Sided) 95% 2.703 to 47.476 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | KdD/Kd | |
| Title | Overall Survival |
|---|---|
| Description | Overall survival was defined as the time from randomization until death from any cause. |
| Time Frame | At approximately 230 OS events or 58 months after the first participant is enrolled, whichever occurs earlier. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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 where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal. Treatment-related adverse events are adverse events considered related to at least one investigational product by the investigator, including those with unknown relationship. |
| Time Frame | From Day 1 until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 153 | 308 |
| All TEAEs |
147
95.5%
|
306
98.1%
|
| TEAEs: Severity Grade >=3 |
113
73.4%
|
253
81.1%
|
| TEAEs: Serious Adverse Events |
70
45.5%
|
173
55.4%
|
| TEAEs: Leading to discontinuation of carfilzomib |
33
21.4%
|
65
20.8%
|
| TEAEs: Leading to discontinuation of daratumumab |
NA
NaN
|
28
9%
|
| TEAEs: Leading to discon of dexamethasone |
37
24%
|
33
10.6%
|
| Fatal TEAEs |
8
5.2%
|
30
9.6%
|
| Treatment-related TEAEs |
129
83.8%
|
260
83.3%
|
| Related TEAEs: Grade >=3 |
74
48.1%
|
187
59.9%
|
| Related and serious TEAEs: |
32
20.8%
|
84
26.9%
|
| Related TEAEs: discon of carfilzomib |
21
13.6%
|
50
16%
|
| Related TEAEs: discon of daratumumab |
NA
NaN
|
15
4.8%
|
| Related TEAEs: discon of dexamethasone |
24
15.6%
|
19
6.1%
|
| Related Fatal TEAEs |
0
0%
|
5
1.6%
|
| Title | Kaplan-Meier Estimate for Duration of Response (DOR) (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | Duration of response (DOR) was defined as the time (in months) from first evidence of partial response (PR) or better per IMWG-URC 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. |
| Time Frame | Day 1 until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants Who Responded in the Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 115 | 263 |
| Median (95% Confidence Interval) [months] |
16.6
|
NA
|
| Title | Kaplan-Meier Estimate for Time to Next Treatment (TTNT) (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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. |
| Time Frame | From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Median (95% Confidence Interval) [months] |
17.3
|
NA
|
| Title | Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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. |
| Time Frame | From randomization until the data cut-off date of 14 July 2019; as of the data cut-off date, a median of 40.29 weeks of treatment (any study drug) in the Kd group and 70.14 weeks of treatment (any study drug) in the KdD group |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Median (95% Confidence Interval) [months] |
17.5
|
NA
|
| Title | 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 (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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. |
| Time Frame | Randomization to Months 3, 6, 12, and 18 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| 3 months |
90.0
58.4%
|
95.3
30.5%
|
| 6 months |
79.4
51.6%
|
86.4
27.7%
|
| 12 months |
62.7
40.7%
|
77.5
24.8%
|
| 18 months |
45.1
29.3%
|
68.5
22%
|
| Title | Time to Overall Response as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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. |
| Time Frame | From randomization until the data cut-off date of 14 July 2019; the maximum time to response was 14 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants Who Responded in the Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 115 | 263 |
| Mean (Standard Deviation) [months] |
1.5
(1.1)
|
1.4
(1.4)
|
| Title | Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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) for 12 months or more after achieving MRD[-]CR status. 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method. |
| Time Frame | Month 8 to 25 months (maximum time as of data cut-off) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Number (95% Confidence Interval) [percentage of participants] |
0.0
0%
|
0.0
0%
|
| Title | Time to Complete Response (CR) as Assessed by the Independent Review Committee (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | Time to complete response was defined as the time from randomization to the earliest date a response of strict complete response (sCR) or complete response (CR) per IMWG-URC is first achieved and subsequently confirmed. |
| Time Frame | From randomization until the data cut-off date of 14 July 2019; the maximum time to CR was 16 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants Who had a CR in the Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 16 | 89 |
| Mean (Standard Deviation) [months] |
7.5
(3.4)
|
8.7
(3.1)
|
| Title | Percentage of Participants Who Achieved Minimal Residual Disease Negative (MRD[-]) Status as Assessed by Next Generation Sequencing at 12 Months |
|---|---|
| Description | MRD[-] at 12-month was defined as achievement of MRD[-] status as assessed by next-generation sequencing (NGS) 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. |
| Time Frame | 12 Months (8- to 13-month window) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Number (95% Confidence Interval) [percentage of participants] |
3.9
2.5%
|
17.6
5.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Comments | Odds ratios and corresponding 95% CIs were estimated by a stratified analysis using the Mantel-Haenszel method. P-values were calculated using the stratified Cochran-Mantel-Haenszel Chi-Square test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sided p-value | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 5.762 | |
| Confidence Interval |
(2-Sided) 95% 2.375 to 13.979 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | KdD/Kd | |
| Title | 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 (Data Cut-off Date 14 July 2019) |
|---|---|
| Description | 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). (data cut-off date 14 July 2019) |
| Time Frame | Baseline (Day 1 pre-dose) up to Week 102 (maximum treatment by cut-off) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population |
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. |
| Measure Participants | 154 | 312 |
| Baseline |
66.19
(19.19)
|
61.64
(20.50)
|
| Cycle 2 |
64.35
(16.25)
|
60.98
(19.68)
|
| Cycle 3 |
66.13
(18.12)
|
63.17
(18.29)
|
| Cycle 4 |
66.67
(15.01)
|
63.47
(18.06)
|
| Cycle 5 |
67.62
(17.19)
|
64.45
(16.76)
|
| Cycle 6 |
68.06
(15.80)
|
65.92
(16.85)
|
| Cycle 7 |
69.30
(14.60)
|
65.81
(16.63)
|
| Cycle 8 |
69.44
(17.82)
|
66.34
(16.64)
|
| Cycle 9 |
65.72
(15.90)
|
67.73
(15.54)
|
| Cycle 10 |
68.38
(14.56)
|
67.89
(16.27)
|
| Cycle 11 |
67.42
(15.24)
|
68.38
(17.43)
|
| Cycle 12 |
65.13
(14.94)
|
67.38
(17.16)
|
| Cycle 13 |
67.49
(16.51)
|
67.00
(18.21)
|
| Cycle 14 |
67.66
(17.03)
|
66.12
(16.60)
|
| Cycle 15 |
69.34
(15.31)
|
67.84
(17.63)
|
| Cycle 16 |
68.55
(16.40)
|
66.56
(18.68)
|
| Cycle 17 |
70.19
(14.70)
|
69.93
(15.45)
|
| Cycle 18 |
65.48
(16.23)
|
66.02
(15.59)
|
| Cycle 19 |
66.94
(17.16)
|
68.41
(16.57)
|
| Cycle 20 |
69.27
(11.27)
|
64.68
(17.29)
|
| Cycle 21 |
69.70
(14.56)
|
67.44
(14.86)
|
| Cycle 22 |
75.00
(9.62)
|
67.67
(17.57)
|
| Cycle 23 |
70.83
(5.89)
|
68.75
(19.36)
|
| Cycle 24 |
75.00
(11.79)
|
63.89
(13.18)
|
| Cycle 25 |
75.00
(11.79)
|
62.96
(18.22)
|
| Cycle 26 |
79.17
(17.68)
|
|
| Follow-up |
64.58
(10.49)
|
70.00
(21.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab |
|---|---|---|
| Comments | Analysis was performed based on a linear mixed effects model. The model included fixed effects of treatment (all baseline responses were modeled with a dummy treatment), baseline QLQ-C30 GHS/QoL score, randomization stratification factors (ISS stage at screening (Stage 1 or 2 vs Stage 3), prior proteasome inhibitor exposure (yes vs no), number of prior lines of therapy (1 vs . 2)), random effects of subject intercept and random slope of time. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9637 |
| Comments | ||
| Method | linear mixed effects model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.06 | |
| Confidence Interval |
() 95% -2.39 to 2.50 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.24 |
|
| Estimation Comments | The overall treatment difference (KdD - Kd) | |
Adverse Events
| Time Frame | Mortality - Death that occurred from the date of enrollment until the data cutoff of 14 July 2019. Treatment-emergent adverse events - any adverse events with an onset after the administration of the first dose of any study treatment and 30 days of the last dose of any study treatment, or the data cutoff of 14 July 2019, whichever occurs earlier. The longest treatment duration as of the data cut-off was 102.3 weeks while on carfilzomib. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. | |||
| Arm/Group Title | Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab | ||
| Arm/Group Description | 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. | 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 dosage was continued on Cycles 7+: day 1 only. | ||
All Cause Mortality |
||||
| Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 36/154 (23.4%) | 59/312 (18.9%) | ||
Serious Adverse Events |
||||
| Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/153 (45.8%) | 173/308 (56.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/153 (0.7%) | 7/308 (2.3%) | ||
| Febrile neutropenia | 1/153 (0.7%) | 2/308 (0.6%) | ||
| Pancytopenia | 1/153 (0.7%) | 0/308 (0%) | ||
| Plasmacytosis | 0/153 (0%) | 1/308 (0.3%) | ||
| Thrombocytopenia | 1/153 (0.7%) | 5/308 (1.6%) | ||
| Thrombotic thrombocytopenic purpura | 2/153 (1.3%) | 2/308 (0.6%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Acute myocardial infarction | 0/153 (0%) | 2/308 (0.6%) | ||
| Angina pectoris | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Arteriosclerosis coronary artery | 1/153 (0.7%) | 0/308 (0%) | ||
| Arteriospasm coronary | 0/153 (0%) | 1/308 (0.3%) | ||
| Atrial fibrillation | 1/153 (0.7%) | 5/308 (1.6%) | ||
| Atrial flutter | 0/153 (0%) | 2/308 (0.6%) | ||
| Cardiac arrest | 0/153 (0%) | 3/308 (1%) | ||
| Cardiac failure | 4/153 (2.6%) | 4/308 (1.3%) | ||
| Cardiac failure acute | 2/153 (1.3%) | 2/308 (0.6%) | ||
| Cardiac failure congestive | 0/153 (0%) | 1/308 (0.3%) | ||
| Cardio-respiratory arrest | 0/153 (0%) | 1/308 (0.3%) | ||
| Cardiomyopathy | 0/153 (0%) | 1/308 (0.3%) | ||
| Coronary artery disease | 0/153 (0%) | 1/308 (0.3%) | ||
| Extrasystoles | 1/153 (0.7%) | 0/308 (0%) | ||
| Myocardial infarction | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Myocardial ischaemia | 0/153 (0%) | 2/308 (0.6%) | ||
| Tachycardia | 0/153 (0%) | 1/308 (0.3%) | ||
| Endocrine disorders | ||||
| Thyroid mass | 1/153 (0.7%) | 0/308 (0%) | ||
| Eye disorders | ||||
| Cataract | 1/153 (0.7%) | 3/308 (1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/153 (0.7%) | 0/308 (0%) | ||
| Colitis | 1/153 (0.7%) | 0/308 (0%) | ||
| Diarrhoea | 0/153 (0%) | 5/308 (1.6%) | ||
| Diverticular perforation | 0/153 (0%) | 1/308 (0.3%) | ||
| Gastritis | 0/153 (0%) | 1/308 (0.3%) | ||
| Inguinal hernia | 0/153 (0%) | 1/308 (0.3%) | ||
| Intra-abdominal haemorrhage | 1/153 (0.7%) | 0/308 (0%) | ||
| Rectal haemorrhage | 1/153 (0.7%) | 0/308 (0%) | ||
| Upper gastrointestinal haemorrhage | 0/153 (0%) | 2/308 (0.6%) | ||
| General disorders | ||||
| Asthenia | 0/153 (0%) | 1/308 (0.3%) | ||
| Chest pain | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Death | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Fatigue | 0/153 (0%) | 3/308 (1%) | ||
| Hyperthermia | 0/153 (0%) | 1/308 (0.3%) | ||
| Malaise | 0/153 (0%) | 1/308 (0.3%) | ||
| Peripheral swelling | 1/153 (0.7%) | 0/308 (0%) | ||
| Pyrexia | 3/153 (2%) | 12/308 (3.9%) | ||
| Sudden death | 0/153 (0%) | 2/308 (0.6%) | ||
| Unevaluable event | 0/153 (0%) | 1/308 (0.3%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 0/153 (0%) | 1/308 (0.3%) | ||
| Cholecystitis acute | 0/153 (0%) | 1/308 (0.3%) | ||
| Hepatic function abnormal | 0/153 (0%) | 2/308 (0.6%) | ||
| Hepatitis toxic | 0/153 (0%) | 1/308 (0.3%) | ||
| Venoocclusive liver disease | 1/153 (0.7%) | 0/308 (0%) | ||
| Infections and infestations | ||||
| Acinetobacter infection | 0/153 (0%) | 1/308 (0.3%) | ||
| Arthritis bacterial | 1/153 (0.7%) | 0/308 (0%) | ||
| Bacteraemia | 0/153 (0%) | 2/308 (0.6%) | ||
| Bronchitis | 0/153 (0%) | 6/308 (1.9%) | ||
| Campylobacter infection | 1/153 (0.7%) | 0/308 (0%) | ||
| Catheter site abscess | 0/153 (0%) | 1/308 (0.3%) | ||
| Cellulitis | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Chronic sinusitis | 0/153 (0%) | 1/308 (0.3%) | ||
| Clostridium difficile infection | 1/153 (0.7%) | 0/308 (0%) | ||
| Device related infection | 1/153 (0.7%) | 2/308 (0.6%) | ||
| Diarrhoea infectious | 0/153 (0%) | 1/308 (0.3%) | ||
| Enterocolitis infectious | 0/153 (0%) | 1/308 (0.3%) | ||
| Erysipelas | 0/153 (0%) | 1/308 (0.3%) | ||
| Gastroenteritis | 2/153 (1.3%) | 1/308 (0.3%) | ||
| Gastroenteritis salmonella | 0/153 (0%) | 1/308 (0.3%) | ||
| Herpes zoster | 0/153 (0%) | 1/308 (0.3%) | ||
| Infection | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Influenza | 2/153 (1.3%) | 12/308 (3.9%) | ||
| Lower respiratory tract infection | 1/153 (0.7%) | 5/308 (1.6%) | ||
| Lung infection | 1/153 (0.7%) | 2/308 (0.6%) | ||
| Meningitis pneumococcal | 1/153 (0.7%) | 0/308 (0%) | ||
| Nasopharyngitis | 0/153 (0%) | 1/308 (0.3%) | ||
| Otitis media acute | 0/153 (0%) | 1/308 (0.3%) | ||
| Peritonitis | 1/153 (0.7%) | 0/308 (0%) | ||
| Picornavirus infection | 1/153 (0.7%) | 0/308 (0%) | ||
| Pneumococcal sepsis | 0/153 (0%) | 1/308 (0.3%) | ||
| Pneumocystis jirovecii pneumonia | 0/153 (0%) | 1/308 (0.3%) | ||
| Pneumonia | 14/153 (9.2%) | 38/308 (12.3%) | ||
| Pneumonia bacterial | 0/153 (0%) | 1/308 (0.3%) | ||
| Pneumonia cytomegaloviral | 0/153 (0%) | 1/308 (0.3%) | ||
| Pneumonia mycoplasmal | 0/153 (0%) | 1/308 (0.3%) | ||
| Pneumonia respiratory syncytial viral | 0/153 (0%) | 1/308 (0.3%) | ||
| Pneumonia viral | 2/153 (1.3%) | 0/308 (0%) | ||
| Respiratory syncytial virus infection | 0/153 (0%) | 3/308 (1%) | ||
| Respiratory tract infection | 2/153 (1.3%) | 5/308 (1.6%) | ||
| Respiratory tract infection viral | 1/153 (0.7%) | 0/308 (0%) | ||
| Rhinovirus infection | 1/153 (0.7%) | 0/308 (0%) | ||
| Sepsis | 2/153 (1.3%) | 12/308 (3.9%) | ||
| Septic shock | 2/153 (1.3%) | 5/308 (1.6%) | ||
| Sinusitis | 0/153 (0%) | 1/308 (0.3%) | ||
| Skin infection | 0/153 (0%) | 1/308 (0.3%) | ||
| Staphylococcal infection | 0/153 (0%) | 1/308 (0.3%) | ||
| Streptococcal bacteraemia | 0/153 (0%) | 1/308 (0.3%) | ||
| Streptococcal sepsis | 0/153 (0%) | 1/308 (0.3%) | ||
| Thrombophlebitis septic | 0/153 (0%) | 1/308 (0.3%) | ||
| Upper respiratory tract infection | 1/153 (0.7%) | 3/308 (1%) | ||
| Urinary tract infection | 3/153 (2%) | 4/308 (1.3%) | ||
| Vascular device infection | 1/153 (0.7%) | 0/308 (0%) | ||
| Viral infection | 0/153 (0%) | 2/308 (0.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 0/153 (0%) | 1/308 (0.3%) | ||
| Femoral neck fracture | 1/153 (0.7%) | 0/308 (0%) | ||
| Femur fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Hip fracture | 1/153 (0.7%) | 0/308 (0%) | ||
| Infusion related reaction | 0/153 (0%) | 3/308 (1%) | ||
| Lower limb fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Overdose | 0/153 (0%) | 2/308 (0.6%) | ||
| Rib fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Spinal compression fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Spinal fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Sternal fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Thoracic vertebral fracture | 2/153 (1.3%) | 0/308 (0%) | ||
| Tracheal obstruction | 0/153 (0%) | 1/308 (0.3%) | ||
| Traumatic fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Venous injury | 1/153 (0.7%) | 0/308 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 0/153 (0%) | 1/308 (0.3%) | ||
| Blood creatinine increased | 0/153 (0%) | 2/308 (0.6%) | ||
| C-reactive protein increased | 0/153 (0%) | 1/308 (0.3%) | ||
| Ejection fraction decreased | 0/153 (0%) | 1/308 (0.3%) | ||
| Haemoglobin abnormal | 0/153 (0%) | 1/308 (0.3%) | ||
| Liver function test increased | 0/153 (0%) | 1/308 (0.3%) | ||
| Medical observation | 1/153 (0.7%) | 0/308 (0%) | ||
| Weight decreased | 0/153 (0%) | 1/308 (0.3%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/153 (0%) | 1/308 (0.3%) | ||
| Fluid overload | 1/153 (0.7%) | 0/308 (0%) | ||
| Hyperglycaemia | 0/153 (0%) | 1/308 (0.3%) | ||
| Hyperkalaemia | 0/153 (0%) | 1/308 (0.3%) | ||
| Hypoglycaemia | 0/153 (0%) | 1/308 (0.3%) | ||
| Hypokalaemia | 0/153 (0%) | 1/308 (0.3%) | ||
| Hyponatraemia | 0/153 (0%) | 1/308 (0.3%) | ||
| Tumour lysis syndrome | 1/153 (0.7%) | 2/308 (0.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/153 (0.7%) | 3/308 (1%) | ||
| Intervertebral disc protrusion | 0/153 (0%) | 1/308 (0.3%) | ||
| Osteolysis | 0/153 (0%) | 1/308 (0.3%) | ||
| Osteonecrosis of jaw | 0/153 (0%) | 2/308 (0.6%) | ||
| Pain in extremity | 1/153 (0.7%) | 0/308 (0%) | ||
| Pathological fracture | 0/153 (0%) | 1/308 (0.3%) | ||
| Spinal disorder | 0/153 (0%) | 1/308 (0.3%) | ||
| Spinal pain | 1/153 (0.7%) | 0/308 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 0/153 (0%) | 1/308 (0.3%) | ||
| Plasma cell myeloma | 5/153 (3.3%) | 7/308 (2.3%) | ||
| Plasmacytoma | 0/153 (0%) | 2/308 (0.6%) | ||
| Squamous cell carcinoma | 0/153 (0%) | 1/308 (0.3%) | ||
| Tumour pain | 0/153 (0%) | 1/308 (0.3%) | ||
| Nervous system disorders | ||||
| Cerebral haemorrhage | 0/153 (0%) | 1/308 (0.3%) | ||
| Cerebrovascular accident | 0/153 (0%) | 2/308 (0.6%) | ||
| Ischaemic stroke | 0/153 (0%) | 1/308 (0.3%) | ||
| Monoparesis | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Optic neuritis | 1/153 (0.7%) | 0/308 (0%) | ||
| Posterior reversible encephalopathy syndrome | 0/153 (0%) | 2/308 (0.6%) | ||
| Spinal cord compression | 1/153 (0.7%) | 0/308 (0%) | ||
| Stupor | 0/153 (0%) | 1/308 (0.3%) | ||
| Syncope | 0/153 (0%) | 2/308 (0.6%) | ||
| Psychiatric disorders | ||||
| Agitation | 0/153 (0%) | 1/308 (0.3%) | ||
| Anxiety | 1/153 (0.7%) | 0/308 (0%) | ||
| Hypomania | 0/153 (0%) | 1/308 (0.3%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 7/153 (4.6%) | 7/308 (2.3%) | ||
| Chronic kidney disease | 1/153 (0.7%) | 1/308 (0.3%) | ||
| Renal failure | 2/153 (1.3%) | 0/308 (0%) | ||
| Renal impairment | 1/153 (0.7%) | 0/308 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 1/153 (0.7%) | 0/308 (0%) | ||
| Bronchial hyperreactivity | 0/153 (0%) | 1/308 (0.3%) | ||
| Bronchopneumopathy | 1/153 (0.7%) | 0/308 (0%) | ||
| Chronic obstructive pulmonary disease | 0/153 (0%) | 1/308 (0.3%) | ||
| Cough | 0/153 (0%) | 1/308 (0.3%) | ||
| Dyspnoea | 5/153 (3.3%) | 4/308 (1.3%) | ||
| Epistaxis | 0/153 (0%) | 1/308 (0.3%) | ||
| Interstitial lung disease | 0/153 (0%) | 3/308 (1%) | ||
| Organising pneumonia | 0/153 (0%) | 1/308 (0.3%) | ||
| Pleural effusion | 1/153 (0.7%) | 3/308 (1%) | ||
| Pneumonitis | 0/153 (0%) | 2/308 (0.6%) | ||
| Pulmonary arterial hypertension | 0/153 (0%) | 1/308 (0.3%) | ||
| Pulmonary embolism | 5/153 (3.3%) | 7/308 (2.3%) | ||
| Pulmonary hypertension | 1/153 (0.7%) | 2/308 (0.6%) | ||
| Pulmonary oedema | 2/153 (1.3%) | 5/308 (1.6%) | ||
| Pulmonary toxicity | 1/153 (0.7%) | 0/308 (0%) | ||
| Respiratory failure | 0/153 (0%) | 3/308 (1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 1/153 (0.7%) | 0/308 (0%) | ||
| Rash maculo-papular | 1/153 (0.7%) | 0/308 (0%) | ||
| Surgical and medical procedures | ||||
| Arteriovenous fistula operation | 0/153 (0%) | 1/308 (0.3%) | ||
| Vascular disorders | ||||
| Aortic stenosis | 0/153 (0%) | 1/308 (0.3%) | ||
| Deep vein thrombosis | 2/153 (1.3%) | 1/308 (0.3%) | ||
| Hypertension | 2/153 (1.3%) | 2/308 (0.6%) | ||
| Hypertensive crisis | 1/153 (0.7%) | 0/308 (0%) | ||
| Poor venous access | 1/153 (0.7%) | 0/308 (0%) | ||
| Venous thrombosis | 0/153 (0%) | 1/308 (0.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Kd - Carfilzomib and Dexamethasone | KdD - Carfilzomib, Dexamethasone and Daratumumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 136/153 (88.9%) | 291/308 (94.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 47/153 (30.7%) | 101/308 (32.8%) | ||
| Leukopenia | 6/153 (3.9%) | 20/308 (6.5%) | ||
| Lymphopenia | 12/153 (7.8%) | 27/308 (8.8%) | ||
| Neutropenia | 15/153 (9.8%) | 43/308 (14%) | ||
| Thrombocytopenia | 45/153 (29.4%) | 115/308 (37.3%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 6/153 (3.9%) | 22/308 (7.1%) | ||
| Diarrhoea | 22/153 (14.4%) | 94/308 (30.5%) | ||
| Nausea | 20/153 (13.1%) | 56/308 (18.2%) | ||
| Vomiting | 13/153 (8.5%) | 37/308 (12%) | ||
| General disorders | ||||
| Asthenia | 17/153 (11.1%) | 29/308 (9.4%) | ||
| Chills | 6/153 (3.9%) | 17/308 (5.5%) | ||
| Fatigue | 28/153 (18.3%) | 74/308 (24%) | ||
| Oedema | 8/153 (5.2%) | 11/308 (3.6%) | ||
| Oedema peripheral | 14/153 (9.2%) | 33/308 (10.7%) | ||
| Pyrexia | 21/153 (13.7%) | 52/308 (16.9%) | ||
| Infections and infestations | ||||
| Bronchitis | 18/153 (11.8%) | 49/308 (15.9%) | ||
| Conjunctivitis | 3/153 (2%) | 16/308 (5.2%) | ||
| Influenza | 9/153 (5.9%) | 23/308 (7.5%) | ||
| Nasopharyngitis | 13/153 (8.5%) | 27/308 (8.8%) | ||
| Pneumonia | 5/153 (3.3%) | 23/308 (7.5%) | ||
| Respiratory tract infection | 8/153 (5.2%) | 29/308 (9.4%) | ||
| Upper respiratory tract infection | 35/153 (22.9%) | 89/308 (28.9%) | ||
| Urinary tract infection | 1/153 (0.7%) | 16/308 (5.2%) | ||
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 3/153 (2%) | 22/308 (7.1%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 9/153 (5.9%) | 27/308 (8.8%) | ||
| Hyperglycaemia | 11/153 (7.2%) | 27/308 (8.8%) | ||
| Hypokalaemia | 9/153 (5.9%) | 18/308 (5.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 8/153 (5.2%) | 26/308 (8.4%) | ||
| Back pain | 14/153 (9.2%) | 48/308 (15.6%) | ||
| Muscle spasms | 18/153 (11.8%) | 36/308 (11.7%) | ||
| Pain in extremity | 9/153 (5.9%) | 19/308 (6.2%) | ||
| Nervous system disorders | ||||
| Dizziness | 4/153 (2.6%) | 23/308 (7.5%) | ||
| Headache | 18/153 (11.8%) | 41/308 (13.3%) | ||
| Neuropathy peripheral | 5/153 (3.3%) | 25/308 (8.1%) | ||
| Peripheral sensory neuropathy | 2/153 (1.3%) | 20/308 (6.5%) | ||
| Psychiatric disorders | ||||
| Insomnia | 17/153 (11.1%) | 55/308 (17.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 30/153 (19.6%) | 51/308 (16.6%) | ||
| Dyspnoea | 33/153 (21.6%) | 60/308 (19.5%) | ||
| Productive cough | 6/153 (3.9%) | 21/308 (6.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 10/153 (6.5%) | 17/308 (5.5%) | ||
| Vascular disorders | ||||
| Hypertension | 40/153 (26.1%) | 93/308 (30.2%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
| medinfo@amgen.com |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT03158688
Other Study ID Numbers:
- 20160275
- 2016-003554-33
First Posted:
May 18, 2017
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022