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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03158688
Ethics application status
Date submitted
9/05/2017
Date registered
18/05/2017
Date last updated
6/12/2019

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 CANDOR Study of Carfilzomib ANd Daratumumab fOr Relapsed 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 or 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: Arm 2 - Carfilzomib and Dexamethasone - Carfilzomib will be dosed twice weekly as an intravenous (IV) infusion and Dexamethasone will be taken orally or by IV infusion weekly. The IV administration of dexamethasone must be given on carfilzomib IV infusion days. The required order of administrationon Arm 2 is as follows: dexamethasone then carfilzomib.
For days when dexamethasone is given in the absence of carfilzomib IV infusion, it may be given orally (PO).

Active Comparator: Arm 1 - Carfilzomib, Dexamethasone and Daratumumab - Carfilzomib will be dosed twice weekly as an intravenous (IV) infusion. Daratumumab will be administered as an IV infusion - on days 1 and 2 of cycle 1 at 8 mg/kg dose each day; then at 16 mg/kg dose once weekly as a single infusion for the remaining doses of the first 2 cycles; then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. Dexamethasone 40 mg will be taken orally or by IV infusion weekly. The IV administration of dexamethasone must be given on carfilzomib and/or daratumumab IV infusion days. On days when more than 1 investigational product is administered, the required order of administration is as follows: dexamethasone, pre-infusion medications for daratumumab, carfilzomib, daratumumab, and post-infusion medications for daratumumab.


Treatment: Drugs: Dexamethasone
Dexamethasone 40 mg will be taken orally or by IV infusion weekly. The IV administration of dexamethasone must be given on carfilzomib and/or daratumumab IV infusion days. Dexamethasone IV will be given on successive days at a split dose of 20 mg each treatment day on weeks with carfilzomib and/or daratumumab infusions. All subjects regardless of age will be required to receive 20 mg of dexamethasone on days 1 and 2 of cycle 1 (as a preinfusion medication for daratumumab infusion) followed by 20 mg of methylprednisolone or equivalent on the third day.

Treatment: Drugs: Daratumumab
Daratumumab will be administered as an IV infusion. On days 1 and 2 of cycle 1, daratumumab will be administered at a split-dose of 8 mg/kg in 500 mL normal saline. The dose of 16 mg/kg in 500 mL normal saline will be given once weekly as a single infusion for the remaining doses of the first 2 cycles (ie, days 8, 15, and 22 of cycle 1; and days 1, 8, 15, and 22 of cycle 2), then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. The administration may be within ± 2 days for each scheduled dose.

Treatment: Drugs: Carfilzomib
Carfilzomib will be administered as an intravenous (IV) infusion. On days when more than 1 investigational product is administered, the required order of administration is as follows: dexamethasone, pre-infusion medications for daratumumab, carfilzomib, daratumumab, and post infusion medications for daratumumab.
Carfilzomib will be dosed twice weekly over 30 ± 5 minutes, on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The administration may be within ± 2 days for each scheduled dose. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 56 mg/m2 beginning on cycle 1 day 8 and thereafter.
Each subject's first dose of carfilzomib will be calculated based upon baseline body surface area (BSA). Dose should be capped based on a BSA of 2.2 m2.

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

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) - Compare carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in terms of progression free survival (PFS) in patients with multiple myeloma who have relapsed after 1 to 3 prior therapies.
Timepoint [1] 0 0
28 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR) - Overall Response Rate (ORR; defined as the proportion of best overall response of stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]).
Timepoint [1] 0 0
28 Months
Secondary outcome [2] 0 0
Rate of minimal residual disease negative-complete response - Rate of minimal residual disease negative-complete response (MRD[-]CR) in bone marrow aspirates at 12 months (± 4 weeks) as determined by Next-Generation sequencing (NGS).
Timepoint [2] 0 0
12 Months
Secondary outcome [3] 0 0
Duration of response (DOR)
Timepoint [3] 0 0
28 Months
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
28, 36, 48 and 58 Months
Secondary outcome [5] 0 0
Time to next treatment
Timepoint [5] 0 0
28 Months
Secondary outcome [6] 0 0
time to progression (TTP)
Timepoint [6] 0 0
28 Months
Secondary outcome [7] 0 0
Time to response
Timepoint [7] 0 0
28 Months
Secondary outcome [8] 0 0
Persistence of MRD[-]CR
Timepoint [8] 0 0
28 Months
Secondary outcome [9] 0 0
Complete response rate (CRR)
Timepoint [9] 0 0
28 Months
Secondary outcome [10] 0 0
MRD[-] rate - MRD[-]CR rate, MRD[-]CR defined as achievement of CR by IRC per International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and MRD[-] status as assessed by NGS (at a 10-5 level, pending analytical validation) at 12 months
Timepoint [10] 0 0
12 Months
Secondary outcome [11] 0 0
Quality of life questionnaire - core 30 items - Quality of life questionnaire - core 30 items (QLQ-C30).
Timepoint [11] 0 0
28 Months
Secondary outcome [12] 0 0
Quality of Life (QoL) measured by European Organization - Quality of Life (QoL) measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3 questionnaire.
Timepoint [12] 0 0
28 Months
Secondary outcome [13] 0 0
Subject incidence of treatment-emergent adverse events
Timepoint [13] 0 0
28 Months

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, see
Appendix E for guidance)

- Criteria 5 Prior therapy with carfilzomib is allowed as long as the patient had at
least a 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
Gender
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 x 109/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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Research Site - Liverpool
Recruitment hospital [2] 0 0
Research Site - St Leonards
Recruitment hospital [3] 0 0
Research Site - Westmead
Recruitment hospital [4] 0 0
Research Site - Herston
Recruitment hospital [5] 0 0
Research Site - Woolloongabba
Recruitment hospital [6] 0 0
Research Site - Adelaide
Recruitment hospital [7] 0 0
Research Site - East Melbourne
Recruitment hospital [8] 0 0
Research Site - Fitzroy, VIC
Recruitment hospital [9] 0 0
Research Site - Geelong
Recruitment hospital [10] 0 0
Research Site - 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
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United States of America
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Georgia
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United States of America
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Illinois
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Indiana
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Mississippi
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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South Carolina
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Texas
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Austria
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Graz
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Salzburg
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Belgium
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Antwerpen
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Belgium
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Brussel
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Belgium
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Charleroi
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Gent
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Belgium
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Leuven
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Plovdiv
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Sofia
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Alberta
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Praha 2
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Nantes Cedex 1
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Patra
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Lublin
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Poznan
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Wroclaw
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Romania
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Brasov
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Bucharest
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Bucuresti
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Cluj-Napoca
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Craiova
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Russian Federation
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Nizhny Novgorod
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Russian Federation
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Petrozavodsk
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Russian Federation
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Samara
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Russian Federation
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Saratov
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Spain
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Castilla León
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Cataluña
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Navarra
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Madrid
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Taipei
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Ankara
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Izmir
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Turkey
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Samsun
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United Kingdom
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Leeds
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London
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United Kingdom
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Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
Compare carfizomib, dexamethasone, and daratumumab (KdD) to Carfilzomib and dexamethasone
(Kd) in terms of progression free survival (PFS) in patients with multiple myeloma who have
relapsed after 1 to 3 prior therapies.
Trial website
https://clinicaltrials.gov/show/NCT03158688
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

Summary results
Other publications