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| A randomised comparison of thalidomide and lenalidomide combinations in myeloma patients of all ages |
| ISRCTN | ISRCTN49407852 |
| ClinicalTrials.gov identifier | |
| Public title | A randomised comparison of thalidomide and lenalidomide combinations in myeloma patients of all ages |
| Scientific title | Thalidomide and lenalidomide combinations in newly diagnosed patients with symptomatic myeloma: a randomised, phase III, multi-centre, open-label trial |
| Acronym | Myeloma XI |
| Serial number at source | HM09/8885 |
| Study hypothesis |
Myeloma XI has two treatment pathways; an intensive pathway for younger/fitter patients where intensive high-dose therapy (HDT) with stem cell support is considered appropriate, and a non-intensive pathway for older/less fit patients. The trial aims to answer three main questions at induction, consolidation and maintenance:
1. Is cyclophosphamide-lenalidomide-dexamethasone (RCD) given to maximum response, a better induction regimen than the current UK gold standard of cyclophosphamide-thalidomide-dexamethasone (CTD)? 2. For patients achieving a sub-optimal response to induction across both treatment pathways (less than very good partial response [VGPR]), can the use of bortezomib, cyclophosphamide and dexamethasone (VCD) improve responses and does this translate into improved progression-free survival (PFS) and overall survival (OS)? 3. Can lenalidomide at maintenance improve PFS and OS when compared to the use of no maintenance? CancerHelp UK lay summary for the non-intensive treatment group can be found here: http://www.cancerhelp.org.uk/trials/a-trial-looking-lenalidomide-bortezomib-myeloma-non-intensive-treatment-group-myeloma-XI |
| Lay summary | http://www.cancerhelp.org.uk/trials/a-trial-looking-lenalidomide-bortezomib-intensive-treatment-group-myeloma-XI |
| Ethics approval | Oxfordshire REC A on 17/09/2009 (ref:09/H0604/79) |
| Study design | Randomised phase III multicentre open-label trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Myeloma |
| Participants - inclusion criteria |
1. Aged 18 years or greater, either sex
2. Newly diagnosed as having symptomatic multiple myeloma or non-secretory multiple myeloma based on: 2.1. Paraprotein (M-protein) in serum and/or urine 2.2. Bone marrow clonal plasma cells or plasmacytoma 2.3. Related organ or tissue impairment and/or symptoms considered by the clinician to be myeloma related 3. Provide written informed consent 4. Women of childbearing potential and male patients whose partner is a woman of child bearing potential must be prepared to use contraception in accordance with (and consent to) the Celgene approved process for thalidomide and lenalidomide Risk Management and Pregnancy Prevention, or commit to absolute and continuous abstinence 5. Women of child bearing potential must have a negative pregnancy test in accordance with the Celgene approved process for thalidomide and lenalidomide Risk Management and Pregnancy Prevention |
| Participants - exclusion criteria |
1. Asymptomatic myeloma
2. Solitary plasmacytoma of bone (patients with previous solitary plasmacytoma that have now progressed to symptomatic or non-secretory myeloma are eligible) 3. Extramedullary plasmacytoma (without evidence of myeloma) 4. Previous or concurrent active malignancies, except surgically-removed basal cell carcinoma of the skin or other in situ carcinomas. Patients with remote histories (greater than 5 years) of other cured malignancies may be entered. 5. Previous treatment for myeloma, except the following: 5.1. Local radiotherapy to relieve bone pain or spinal cord compression 5.2. Prior bisphosphonate treatment 5.3. Corticosteroids within the last 3 months 6. Known history of allergy contributable to compounds containing boron or mannitol 7. Grade 2 or greater (National Cancer Institute [NCI] criteria) peripheral neuropathy 8. Caution is advised in patients with a past history of ischaemic heart disease, pericardial disease, acute diffuse infiltrative pulmonary disease or psychiatric disorders, evidence of impaired marrow function or elevated liver function tests, but exclusion is essentially to be at the discretion of the treating clinician 9. Acute renal failure (unresponsive to up to 72 hours of rehydration, characterised by creatinine greater than 500 µmol/l or urine output less than 400 ml/day or requirement for dialysis) |
| Anticipated start date | 01/10/2009 |
| Anticipated end date | 30/09/2017 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 1865 |
| Interventions |
Intensive pathway:
Patients will be initially randomised to receive either CTD (cyclophosphamide, thalidomide and dexamethasone) or RCD (cyclophsphamide, lenalidomide and dexamethasone) and will receive a minimum of 4 cycles of induction chemotherapy to maximum response or patient intolerance. All patients showing a complete response (CR) or very good partial response (VGPR) to RCD/CTD will proceed to peripheral blood stem cell harvest and standard high-dose melphalan (HDM) with supporting autologous peripheral blood stem cell transplant (ASCT). Patients showing a partial response (PR) or minimal response (MR) to RCD/CTD will be randomised to receive consolidation bortezomib plus cyclophosphamide and dexamethasone (VCD) to maximum response or intolerance (up to 8 cycles), or proceed straight to peripheral blood stem cell harvest and standard HDM with supporting ASCT. Once randomised patients have received VCD, they will proceed with harvest, HDM and ASCT. Patients showing progressive disease (PD) or no change (NC) during induction chemotherapy (RCD or CTD) will all receive consolidation VCD (ie will not undergo the VCD vs nothing randomisation) to maximum response or intolerance (up to 8 cycles), then proceed to peripheral blood stem cell harvest and standard HDM with supporting ASCT. Following HDM/ASCT, all patients who are disease progression-free (except those who demonstrated PD or NC during RCD) will undergo maintenance randomisation to either lenalidomide maintenance or no maintenance treatment. Patients randomised to lenalidomide maintenance will commence lenalidomide approximately 100 days post HDM/ASCT. In the absence of toxicity, lenalidomide maintenance will continue (21 days out of every 28) until disease progression. Non-intensive pathway: Patients will be randomised to RCDa (RCD with a reduced dose of dexamethasone) or CTDa (CTD with a reduced dose of dexamethasone and lower starting dose of thalidomide) and will receive a minimum 6 cycles of their randomised induction treatment regimen to maximum response. All patients showing CR or VGPR will proceed to maintenance randomisation (lenalidomide or no maintenance). Patients showing PR or MR to RCDa/CTDa will be randomised to receive consolidation VCD to maximum response or intolerance (up to 8 cycles), or proceed to maintenance randomisation. Once randomised patients have received VCD, they will proceed with maintenance randomisation. Patients showing progressive disease (PD) or NC during induction chemotherapy (RCDa or CTDa) will all receive consolidation VCD (i.e., will not undergo the VCD versus nothing randomisation) to maximum response or intolerance (up to 8 cycles). Following RCD/CTD/VCD, all patients who are disease progression-free (except those who demonstrated PD or NC during RCDa) will undergo maintenance randomisation to either lenalidomide maintenance or no maintenance treatment. In the absence of toxicity, lenalidomide maintenance will continue (21 days out of every 28) until disease progression. |
| Primary outcome measure(s) |
1. Overall survival
2. Progression-free survival Interim analyses will be presented to the DMEC at approximately yearly intervals and the trial will have a formal interim analysis when half the total number of deaths has been observed. No other formal analyses are planned until after the trial is closed to accrual. |
| Secondary outcome measure(s) |
1. Response
2. Conversion rate to CR/VGPR for patients who undergo VCD randomisation 3. Toxicity Interim analyses will be presented to the DMEC at approximately yearly intervals and the trial will have a formal interim analysis when half the total number of deaths has been observed. No other formal analyses are planned until after the trial is closed to accrual. |
| Sources of funding |
1. Cancer Research UK (CRUK) (UK) (ref: CRUK/09/014)
2. Celgene Ltd (UK) |
| Trial website | |
| Publications | |
| Contact name | Prof Gareth Morgan |
| Address |
Section of Haemato-oncology
Brookes Lawley Building The Institute of Cancer Research 15 Cotswold Road Belmont |
| City/town | Sutton |
| Zip/Postcode | SM2 5NG |
| Country | United Kingdom |
| Sponsor | University of Leeds (UK) |
| Address |
c/o Clare Skinner
Research Office Room 10.110, Level 10 Worsley Building |
| City/town | Leeds |
| Zip/Postcode | LS2 9JT |
| Country | United Kingdom |
| Sponsor website: | http://www.leeds.ac.uk |
| Date applied | 24/04/2009 |
| Last edited | 20/12/2011 |
| Date ISRCTN assigned | 29/06/2009 |
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| © 2012 ISRCTN unless otherwise stated. | |
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