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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01818752




Registration number
NCT01818752
Ethics application status
Date submitted
12/02/2013
Date registered
26/03/2013
Date last updated
26/08/2019

Titles & IDs
Public title
Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma
Scientific title
A Randomized, Open-label Phase 3 Study of Carfilzomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma
Secondary ID [1] 0 0
2012-005283-97
Secondary ID [2] 0 0
2012-005
Universal Trial Number (UTN)
Trial acronym
CLARION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - Carfilzomib
Treatment: Drugs - Bortezomib
Treatment: Drugs - Melphalan
Treatment: Drugs - Prednisone

Experimental: Carfilzomib, Melphalan, Prednisone - Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Active comparator: Bortezomib, Melphalan, Prednisone - Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².


Treatment: Drugs: Carfilzomib
Carfilzomib was administered over 30 minutes on days 1, 2, 8, 9, 22, 23, 29, and 30 for nine 42-day cycles. Carfilzomib 20 mg/m² IV was administered on days 1 and 2 of cycle 1, followed by escalation to 36 mg/m² IV starting on day 8 of cycle 1.

Treatment: Drugs: Bortezomib
Bortezomib 1.3 mg/m² was administered as a bolus IV injection or as a subcutaneous injection (per investigator's choice, dose modification, or regulatory approval) on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycles 1 to 4, and on days 1, 8, 22, and 29 of cycles 5 to 9.

Treatment: Drugs: Melphalan
Melphalan 9 mg/m² was taken orally on days 1 to 4 of all cycles.

Treatment: Drugs: Prednisone
Prednisone 60 mg/m² was taken orally on days 1 to 4 of all cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively.
Secondary outcome [2] 0 0
Overall Response Rate
Timepoint [2] 0 0
Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
Secondary outcome [3] 0 0
Complete Response Rate
Timepoint [3] 0 0
Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
Secondary outcome [4] 0 0
Percentage of Participants With = Grade 2 Peripheral Neuropathy
Timepoint [4] 0 0
From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.
Secondary outcome [5] 0 0
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores
Timepoint [5] 0 0
Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48
Secondary outcome [6] 0 0
Number of Participants With Adverse Events
Timepoint [6] 0 0
From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.

Eligibility
Key inclusion criteria
1. Newly diagnosed symptomatic multiple myeloma (per International Myeloma Working Group [IMWG] diagnostic criteria)
2. Transplant ineligibility
3. Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to randomization):

* Serum M-protein = 0.5 g/dL, or
* Urine M-protein = 200 mg/24 hours, or
* In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ratio (SFLC kappa lambda ratio < 0.26 or > 1.65)
4. No prior treatment for multiple myeloma
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Multiple myeloma of IgM (immunoglobulin M) subtype
2. Glucocorticoid therapy within 14 days prior to randomization that equals or exceeds a cumulative dose of 160 mg of dexamethasone
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
4. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
5. Waldenström macroglobulinemia (WM)
6. Known amyloidosis

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
8/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/11/2016
Sample size
Target
Accrual to date
Final
955
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Central Coast Local Health District - North Gosford
Recruitment hospital [4] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Eastern Health - Box Hill Hospital - Box Hill
Recruitment hospital [7] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [8] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [9] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [10] 0 0
Royal North Shore Hospital, Haematology Department - New South Wales
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
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2010 - Darlinghurst
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2250 - North Gosford
Recruitment postcode(s) [4] 0 0
2298 - Waratah
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5000 - Adelaide
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3128 - Box Hill
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- Fitzroy
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3004 - Melbourne
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3690 - Wodonga
Recruitment postcode(s) [10] 0 0
- New South Wales
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective was to compare the progression-free survival of transplant ineligible patients newly diagnosed with multiple myeloma who were treated with carfilzomib, melphalan and prednisone (CMP) or with Velcade® (bortezomib), melphalan and prednisone (VMP).
Trial website
https://clinicaltrials.gov/study/NCT01818752
Trial related presentations / publications
Chari A, Stewart AK, Russell SD, Moreau P, Herrmann J, Banchs J, Hajek R, Groarke J, Lyon AR, Batty GN, Ro S, Huang M, Iskander KS, Lenihan D. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv. 2018 Jul 10;2(13):1633-1644. doi: 10.1182/bloodadvances.2017015545.
Facon T, Lee JH, Moreau P, Niesvizky R, Dimopoulos M, Hajek R, Pour L, Jurczyszyn A, Qiu L, Klippel Z, Zahlten-Kumeli A, Osman M, Paiva B, San-Miguel J. Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 2019 May 2;133(18):1953-1963. doi: 10.1182/blood-2018-09-874396. Epub 2019 Feb 28.
Rosenthal A, Luthi J, Belohlavek M, Kortum KM, Mookadam F, Mayo A, Fonseca R, Bergsagel PL, Reeder CB, Mikhael JR, Stewart AK. Carfilzomib and the cardiorenal system in myeloma: an endothelial effect? Blood Cancer J. 2016 Jan 15;6(1):e384. doi: 10.1038/bcj.2015.112.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01818752