A phase II randomised trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs cyclophosphamide, velcade and dexamethasone (CVD) for first relapse or primary refractory multiple myeloma
| ISRCTN | ISRCTN17354232 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17354232 |
| EudraCT/CTIS number | 2012-001320-36 |
| Secondary identifying numbers | 12956 |
- Submission date
- 12/12/2012
- Registration date
- 12/12/2012
- Last edited
- 14/01/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
http://www.cancerresearchuk.org/cancer-help/trials/a-trial-looking-carfilzomib-myeloma-muk5
Contact information
Dr Sadie Roberts
Scientific
Scientific
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom
| Phone | +44 (0)113 343 9645 |
|---|---|
| s.n.roberts@leeds.ac.uk |
Study information
| Study design | Randomised interventional phase II treatment study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A phase II randomised trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs cyclophosphamide, velcade and dexamethasone (CVD) for first relapse or primary refractory multiple myeloma |
| 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. |
| Ethics approval(s) | ref: 12/LO/1078 |
| Condition | Haematological Oncology; Myeloma |
| Intervention | CCD, Carfilzomib, Cyclophosphamide, Dexamethasone; CVD, Cyclophosphamide, Velcade, Dexamethasone |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | CCD, Carfilzomib, Cyclophosphamide, Dexamethasone; CVD, Cyclophosphamide, Velcade, Dexamethasone |
| Primary outcome measure | Proportion of participants achieving at least VGPR measured at 24 weeks post initial randomisation |
| Secondary outcome measures | Progression-free survival |
| Overall study start date | 01/01/2013 |
| Overall study end date | 30/09/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | UK Sample Size: 300 |
| Total final enrolment | 300 |
| 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 02 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 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 34, 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 Investigators opinion, may interfere with protocol adherence or a participants ability to give informed consent |
| Recruitment start date | 01/01/2013 |
| Recruitment end date | 31/12/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Leeds
Leeds
LS2 9NG
United Kingdom
LS2 9NG
United Kingdom
Sponsor information
University of Leeds (UK)
University/education
University/education
Woodhouse Lane
Leeds
LS2 9JT
England
United Kingdom
| Website | http://www.leeds.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/024mrxd33 |
Funders
Funder type
Charity
Myeloma UK ref: CD11/06
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/03/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | Planned publication in Q1 2021. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository, the MUK 5 Clinical Macro Database hosted by the University of Leeds. The sharing of pseudo-anonymised data will be evaluated on completion of a data access request that should be sent to medctco@leeds.ac.uk and will be reviewed by the trial management group in the first instance. Only requests that have a methodologically sound proposal and whose proposed use of the data has been approved by the independent trial steering committee will be considered. Requests must be fully funded, have appropriate ethical approval and if approved undertake a data-sharing agreement. Consent has been obtained from participants for use of this data in future research. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 17/05/2016 | Yes | No | |
| Abstract results | results presented at ASH | 07/12/2017 | No | No | |
| Basic results | 12/01/2021 | 12/01/2021 | No | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN17354232_BasicResults_12Jan21.pdf
- Uploaded 12/01/2021
Editorial Notes
14/01/2021: Contact details updated.
13/01/2021: Publication and dissemination plan and IPD sharing statement added. Contact details updated.
12/01/2021: The basic results of this trial have been uploaded as an additional file.
03/09/2019: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
21/12/2016: The overall trial end date has been updated from 31/12/2015 to 30/09/2018.
19/05/2016: Publication reference added.
