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Myelomatosis therapy trial for patients of all age groups
ISRCTN ISRCTN68454111
DOI 10.1186/ISRCTN68454111
ClinicalTrials.gov identifier
EudraCT number
Public title Myelomatosis therapy trial for patients of all age groups
Scientific title
Acronym MRC Myeloma IX
Serial number at source G0100132
Study hypothesis 1. Therapeutic questions within the intensive pathway:
1. 1. To compare an oral induction regimen containing thalidomide with a standard infusional induction chemotherapy, CTD versus CVAD, with respect to overall/progression-free survival and response.
1.2. To investigate the effects of giving additional consolidation therapy in the form of a low intensity conditioning allogeneic stem cell transplantation on survival.

2. Therapeutic questions within the non-intensive pathway:
2.1. To compare attenuated C-Thal-Dex (CTDa) with standard MP with respect to overall/progression-free survival and response.

3. Therapeutic questions across both pathways:
3.1. To assess the value of low dose thalidomide in maintenance in improving overall and progression-free survival.
3.2. To compare an aminobisphosphonate, zoledronic acid, with standard clodronate on the severity of bone disease and in improving survival.
3.3. To investigate quality of life in the short-term (during induction chemotherapy/bisphosphonate treatment) and in the long-term (during maintenance therapy).
3.4. To investigate prognostic factors for outcome.

4. Biological objectives:
4.1. To determine the clinical relevance of genetic/cytogenetic changes present at presentation in the definition of prognostic groups.
4.2. To determine the relevance of cellular phenotypes at presentation and to subsequently use these data to monitor residual disease.
4.3. To evaluate serum free light chain (flc) measurement as a prognostic factor and in monitoring disease.
Lay summary http://cancerhelp.cancerresearchuk.org/trials/a-trial-comparing-treatments-for-myeloma
Ethics approval Not provided at time of registration
Study design Randomised controlled trial
Countries of recruitment New Zealand, South Africa, United Kingdom
Disease/condition/study domain Multiple Myeloma
Participants - inclusion criteria 1. Aged 18 years or greater
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
3. Written informed consent
4. Prepared to use contraception
5. Negative pregnancy test
Participants - exclusion criteria 1. Asymptomatic myeloma
2. Solitary plasmacytoma of bone
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
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. low-dose corticosteroids (up to 12 mg/day dexamethasone or 80 mg/day prednisolone, for 14 days)
5.4. up to four single doses of corticosteroids (total dose 1 g methylperdnisolone, 200 mg dexamethasone, or 1.25 g prenisolone)
Caution is advised in patients with a past history of ischaemic heart disease or psychiatric disorders, but exclusion is essentially to be at the discretion of the treating clinician.
6. Acute renal failure (unresponsive to up to 72 h of rehydration characterised by creatine >500 µmol/l or urine output <400 ml/day or requirement for dialysis). These patients are not eligible for this study but may be eligible for inclusion in MERIT (Myeloma Renal Impairment Trial). NB Patients with serum creatinine >2 x upper limit or normal (or creatinine clearance <20 ml/min) are eligible for Myeloma IX, but bisphosphonates should not be administered until serum creatinine has decreased to <2 x upper limit of normal (or creatinine clearance >30 ml/min)
Anticipated start date 14/05/2003
Anticipated end date 31/07/2014
Status of trial Completed
Patient information material Not available in web format, please use the contact details below to request a patient information sheet
Target number of participants 1930
Interventions There are two main pathways:
1. Intensive for 'younger/fitter' patients
2. Non-intensive for 'older/less fit' patients
There are three randomised comparisons within each pathway.

1. Intensive pathway
At diagnosis:
1.1. Cyclophosphamide, vincristine, adriamycin, dexamethasone (CVAD) versus cyclophosphamide, thalidomide, dexamethasone (CTD)
1.2. Clodronate versus Zoledronic acid
After high dose consolidation therapy (HDT):
1.3. Thalidomide versus no maintenance therapy
In addition, following standard high dose melphalan with autograft, patients with an available tissue-compatible sibling donor may be offered a reduced intensity conditioning allograft, if appropriate.

2. Non-intensive pathway
At diagnosis:
2.1. Melphalan, prednisolone (MP) versus cyclophosphamide, thalidomide, dexamethasone (attenuated) (CTDa)
2.2. Clodronate versus Zoledronic acid
After achievement of plateau state:
2.3. Thalidomide versus no maintenance therapy
Primary outcome measure(s) 1. Overall survival
2. Progression-free survival
3. Response
Secondary outcome measure(s) 1. Quality of Life
2. Skeletal related events
3. Toxicity
4. Thromboembolic events
5. Renal toxicity
6. Haematologic toxicity
7. Graft versus Host Disease (GvHD)
Sources of funding Medical Research Council (MRC) (UK)
Trial website
Publications 1. 2005 interim results in: http://www.ncbi.nlm.nih.gov/pubmed/16166766
2. 2010 results on homozygous deletion mapping in myeloma samples in: http://www.ncbi.nlm.nih.gov/pubmed/20215539
3. 2010 results on genomic profiling of multiple myeloma in: http://www.ncbi.nlm.nih.gov/pubmed/20616218
4. 2010 results on XBP1s levels in multiple myeloma in: http://www.ncbi.nlm.nih.gov/pubmed/20421453
5. 2011 results on CTD initial therapy in: http://www.ncbi.nlm.nih.gov/pubmed/21652683
6. 2011 results on secondary outcomes in: http://www.ncbi.nlm.nih.gov/pubmed/21771568
7. 2011 results and meta-analysis in: http://www.ncbi.nlm.nih.gov/pubmed/22021371
8. 2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/22058209
9. 2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21856767
10. 2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22573403
11. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23995858
12. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23974194
13. 2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24733348
Contact name Ms  Louise  Flanagan
  Address Clinical Trials Research Unit
University of Leeds
  City/town Leeds
  Zip/Postcode LS2 9JT
  Country United Kingdom
  Tel +44 (0)113 343 6441
  Fax +44 (0)113 343 6427
  Email l.m.flanagan@leeds.ac.uk
Sponsor University of Leeds (UK)
  Address c/o Clinical Trials Research Unit (CTRU)
University of Leeds
17 Springfield Mount
  City/town Leeds
  Zip/Postcode LS2 9NG
  Country United Kingdom
Date applied 21/09/2000
Last edited 17/04/2014
Date ISRCTN assigned 21/09/2000
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