Contact information

Type

Scientific

Primary contact

Mrs Sue Bourne

ORCID ID

Contact details

University of Leeds
17 Springfield Mount
Leeds
LS2 9NG
United Kingdom
s.bourne@leeds.ac.uk

Additional identifiers

EudraCT number

2012-001320-36

ClinicalTrials.gov number

Protocol/serial number

12956

Study information

Scientific title

Acronym

Study hypothesis

This is a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib and dexamethasone (CVD) for multiple myeloma patients at first relapse or refractory to no more than 1 line of treatment. Participants will be randomised in a 2:1 ratio in favour of CCD. The proposed study will compare 8 cycles of CVD with 6 cycles of CCD, and will also assess the benefit of maintenance carfilzomib in participants in the CCD arm. Participants in the CCD arm, who have at least stable disease at the end of the initial 6 cycles of CCD, will be randomised to receive maintenance therapy with Carfilzomib or no further treatment. Participants in the CVD arm will not receive maintenance therapy. In order to compare the regimens with regard to activity, the trial has been designed to incorporate two co-primary endpoints: response and progression-free survival.

This allows the trial to:
1. Assess the activity of the regimens after a fixed period of 24 weeks of treatment, i.e. not incorporating the maintenance phase in the CCD arm
2. Compare the activity of the whole CCD regimen with and without maintenance therapy. Additionally, the whole CCD regimen without maintenance will be compared with the CVD regimen, by evaluating the longer term endpoint of progression-free survival (PFS).

The trial is designed to assess the non-inferiority of CCD as compared to CVD in terms of response and the superiority of CCD with maintenance as compared to CCD with no maintenance in terms of progression-free survival. The trial will also explore the non-inferiority of CCD with no maintenance as compared to CVD in terms of PFS.

More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12956

Ethics approval

ref: 12/LO/1078

Study design

Randomised interventional phase II treatment study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Haematological Oncology; Myeloma

Intervention

CCD, Carfilzomib, Cyclophosphamide, Dexamethasone; CVD, Cyclophosphamide, Velcade, Dexamethasone

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

Proportion of participants achieving at least VGPR measured at 24 weeks post initial randomisation

Secondary outcome measures

Progression free survival

Overall trial start date

01/01/2013

Overall trial end date

31/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Syptomatic multiple myeloma and requiring therapy for first relapse or primary refractory disease
2. Measurable disease
3. Age = 18 years
4. Life expectancy = 6 months
5. Eastern Cooperative Oncology Group (ECOG) performance status 0–2
6. Adequate hepatic function, with serum ALT = 3.5 times the upper limit of normal and serum direct bilirubin = 2 mg/dL (34 µmol/L) within 14 days prior to randomisation
7. Absolute neutrophil count (ANC) = 1.0 × 10^9/L within 14 days prior to randomisation (growth factor support is not permitted)
8. Haemoglobin = 8 g/dL (80 g/L) within 14 days prior to randomisation (participants may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines)
9. Platelet count = 75 × 10^9/L (= 50 × 10^9/L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to randomisation. Platelet support is not permitted.
10. Creatinine clearance (CrCl) = 15 mL/minute within 14 days prior to randomisation, either measured or calculated using a standard formula (eg, Cockcroft and Gault)
11. Written informed consent
12. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.
13. Male participants must agree to practice contraception

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 300

Participant exclusion criteria

1. Non-secretory multiple myeloma
2. Extramedullary plasmacytoma (without evidence of myeloma)
3. Received therapy for their first relapsed or primary refractory disease other than local radiotherapy, therapeutic plasma exchange, or dexamethasone up to a maximum of 200mg
4. Pregnant or lactating females
5. Major surgery within 21 days prior to randomisation
6. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomisation
7. Known human immunodeficiency virus infection
8. Active hepatitis B or C infection
9. Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker
10. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomisation
11. Previous or concurrent active malignancy within the past 3 years with the exception of:
11.1 Adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer
11.2. Carcinoma in situ of the cervix or breast
11.3. Prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels
11.4. Cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localised transitional cell carcinoma of the bladder or benign tumours of the adrenal or pancreas
12. Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to randomisation
13. Patients with haemorrhagic cystitis
14. Known history of hypersensitivity to any of the study medications or excipients
15. Participants undergoing active treatment for infiltrative lung disease
16. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment
17. Contraindication to IV hydration programme
18. Participants with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomisation
19. Any other clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a participant’s ability to give informed consent

Recruitment start date

01/01/2013

Recruitment end date

31/12/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Leeds
Leeds
LS2 9NG
United Kingdom

Sponsor information

Organisation

University of Leeds (UK)

Sponsor details

Woodhouse Lane
Leeds
LS2 9JT
United Kingdom

Sponsor type

University/education

Website

http://www.leeds.ac.uk/

Funders

Funder type

Charity

Funder name

Myeloma UK ref: CD11/06

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Editorial Notes