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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03158688




Registration number
NCT03158688
Ethics application status
Date submitted
9/05/2017
Date registered
18/05/2017

Titles & IDs
Public title
Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma.
Scientific 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
Secondary ID [1] 0 0
2016-003554-33
Secondary ID [2] 0 0
20160275
Universal Trial Number (UTN)
Trial acronym
CANDOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed Multiple Myeloma 0 0
Refractory Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Daratumumab
Treatment: Drugs - Carfilzomib

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: Daratumumab
Daratumumab was supplied as a concentrated solution for infusion in single-use vials.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) as Assessed by the Independent Review Committee (PA DCO Only)
Timepoint [1] 0 0
From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary outcome [1] 0 0
Overall Response (OR) as Assessed by the Independent Review Committee (PA DCO Only)
Timepoint [1] 0 0
From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary outcome [2] 0 0
Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee
Timepoint [2] 0 0
12 Months (8- to 13-month window)
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
Up to 58 months after the first participant was enrolled (at FA DCO, a median of 40.29 weeks of treatment [any study drug] in the Kd group and 79.29 weeks of treatment [any study drug] in the KdD group; FA DCO was 15 Apr 2022)
Secondary outcome [4] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [4] 0 0
PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks
Secondary outcome [5] 0 0
Kaplan-Meier Estimate for Duration of Response (DOR) (PA DCO Only)
Timepoint [5] 0 0
From Day 1 until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary outcome [6] 0 0
Kaplan-Meier Estimate for Time to Next Treatment (TTNT)
Timepoint [6] 0 0
PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks
Secondary outcome [7] 0 0
Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (PA DCO Only)
Timepoint [7] 0 0
From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary outcome [8] 0 0
Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only)
Timepoint [8] 0 0
Randomization to Months 3, 6, 12, and 18
Secondary outcome [9] 0 0
Time to Overall Response as Assessed by the Independent Review Committee (PA DCO Only)
Timepoint [9] 0 0
From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary outcome [10] 0 0
Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More
Timepoint [10] 0 0
PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks
Secondary outcome [11] 0 0
Percentage of Participants With a Complete Response (CR) as Assessed by the Independent Review Committee (PA DCO Only)
Timepoint [11] 0 0
From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks
Secondary outcome [12] 0 0
Percentage of Participants Who Achieved Minimal Residual Disease Negative (MRD[-]) Status as Assessed by Next Generation Sequencing at 12 Months
Timepoint [12] 0 0
12 Months (8- to 13-month window)
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Baseline (Day 1 pre-dose) up to 236.3 weeks (longest treatment duration as of the FA DCO)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/04/2022
Sample size
Target
Accrual to date
Final
466
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
St Vincents Hospital Sydney - St Leonards
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Womens Hospital - Herston
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Epworth Healthcare - East Melbourne
Recruitment hospital [8] 0 0
St Vincents Hospital Melbourne - Fitzroy, VIC
Recruitment hospital [9] 0 0
Barwon Health, University Hospital Geelong - Geelong
Recruitment hospital [10] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
3002 - East Melbourne
Recruitment postcode(s) [8] 0 0
3065 - Fitzroy, VIC
Recruitment postcode(s) [9] 0 0
3220 - Geelong
Recruitment postcode(s) [10] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Mississippi
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Austria
State/province [12] 0 0
Graz
Country [13] 0 0
Austria
State/province [13] 0 0
Salzburg
Country [14] 0 0
Belgium
State/province [14] 0 0
Antwerpen
Country [15] 0 0
Belgium
State/province [15] 0 0
Brussel
Country [16] 0 0
Belgium
State/province [16] 0 0
Charleroi
Country [17] 0 0
Belgium
State/province [17] 0 0
Gent
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Plovdiv
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Sofia
Country [21] 0 0
Canada
State/province [21] 0 0
Alberta
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
Czechia
State/province [24] 0 0
Brno
Country [25] 0 0
Czechia
State/province [25] 0 0
Hradec Kralove
Country [26] 0 0
Czechia
State/province [26] 0 0
Ostrava-Poruba
Country [27] 0 0
Czechia
State/province [27] 0 0
Plzen
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha 2
Country [29] 0 0
France
State/province [29] 0 0
La Roche Sur Yon Cedex 9
Country [30] 0 0
France
State/province [30] 0 0
Le Chesnay cedex
Country [31] 0 0
France
State/province [31] 0 0
Lille Cedex
Country [32] 0 0
France
State/province [32] 0 0
Nantes Cedex 1
Country [33] 0 0
France
State/province [33] 0 0
Pessac Cedex
Country [34] 0 0
France
State/province [34] 0 0
Pierre-Benite cedex
Country [35] 0 0
France
State/province [35] 0 0
Poitiers Cedex
Country [36] 0 0
France
State/province [36] 0 0
Vandoeuvre les Nancy Cedex
Country [37] 0 0
Greece
State/province [37] 0 0
Athens
Country [38] 0 0
Greece
State/province [38] 0 0
Patra
Country [39] 0 0
Greece
State/province [39] 0 0
Thessaloniki
Country [40] 0 0
Hungary
State/province [40] 0 0
Bekescsaba
Country [41] 0 0
Hungary
State/province [41] 0 0
Budapest
Country [42] 0 0
Hungary
State/province [42] 0 0
Debrecen
Country [43] 0 0
Hungary
State/province [43] 0 0
Szeged
Country [44] 0 0
Japan
State/province [44] 0 0
Aichi
Country [45] 0 0
Japan
State/province [45] 0 0
Chiba
Country [46] 0 0
Japan
State/province [46] 0 0
Fukuoka
Country [47] 0 0
Japan
State/province [47] 0 0
Gifu
Country [48] 0 0
Japan
State/province [48] 0 0
Gunma
Country [49] 0 0
Japan
State/province [49] 0 0
Kyoto
Country [50] 0 0
Japan
State/province [50] 0 0
Niigata
Country [51] 0 0
Japan
State/province [51] 0 0
Okayama
Country [52] 0 0
Japan
State/province [52] 0 0
Osaka
Country [53] 0 0
Japan
State/province [53] 0 0
Saitama
Country [54] 0 0
Japan
State/province [54] 0 0
Tochigi
Country [55] 0 0
Japan
State/province [55] 0 0
Tokushima
Country [56] 0 0
Japan
State/province [56] 0 0
Tokyo
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Goyang-si, Gyeonggi-do
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Hwasun, Jeollanam-do
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Seoul
Country [60] 0 0
Poland
State/province [60] 0 0
Bialystok
Country [61] 0 0
Poland
State/province [61] 0 0
Chorzow
Country [62] 0 0
Poland
State/province [62] 0 0
Lublin
Country [63] 0 0
Poland
State/province [63] 0 0
Poznan
Country [64] 0 0
Poland
State/province [64] 0 0
Warszawa
Country [65] 0 0
Poland
State/province [65] 0 0
Wroclaw
Country [66] 0 0
Romania
State/province [66] 0 0
Brasov
Country [67] 0 0
Romania
State/province [67] 0 0
Bucharest
Country [68] 0 0
Romania
State/province [68] 0 0
Bucuresti
Country [69] 0 0
Romania
State/province [69] 0 0
Cluj-Napoca
Country [70] 0 0
Romania
State/province [70] 0 0
Craiova
Country [71] 0 0
Russian Federation
State/province [71] 0 0
Nizhny Novgorod
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Petrozavodsk
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Samara
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Saratov
Country [75] 0 0
Spain
State/province [75] 0 0
Castilla León
Country [76] 0 0
Spain
State/province [76] 0 0
Cataluña
Country [77] 0 0
Spain
State/province [77] 0 0
Navarra
Country [78] 0 0
Spain
State/province [78] 0 0
Madrid
Country [79] 0 0
Taiwan
State/province [79] 0 0
Taipei
Country [80] 0 0
Turkey
State/province [80] 0 0
Ankara
Country [81] 0 0
Turkey
State/province [81] 0 0
Izmir
Country [82] 0 0
Turkey
State/province [82] 0 0
Samsun
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Leeds
Country [84] 0 0
United Kingdom
State/province [84] 0 0
London
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03158688