Myelomatosis therapy trial for patients of all age groups

ISRCTN	ISRCTN68454111
DOI	https://doi.org/10.1186/ISRCTN68454111
Secondary identifying numbers	G0100132

Submission date: 21/09/2000
Registration date: 21/09/2000
Last edited: 19/10/2018

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://cancerhelp.cancerresearchuk.org/trials/a-trial-comparing-treatments-for-myeloma

Contact information

Ms Louise Flanagan
Scientific

Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom

Phone	+44 (0)113 343 6441
Email	l.m.flanagan@leeds.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
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	Myelomatosis therapy trial for patients of all age groups
Study acronym	MRC Myeloma IX
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.
Ethics approval(s)	Not provided at time of registration
Condition	Multiple Myeloma
Intervention	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
Intervention type	Other
Primary outcome measure	1. Overall survival 2. Progression-free survival 3. Response
Secondary outcome measures	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)
Overall study start date	14/05/2003
Overall study end date	31/07/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	1930
Participant 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
Participant 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)
Recruitment start date	14/05/2003
Recruitment end date	31/07/2014

Locations

Countries of recruitment

England
New Zealand
South Africa
United Kingdom

Study participating centre

Clinical Trials Research Unit

Leeds
LS2 9JT
United Kingdom

Sponsor information

University of Leeds (UK)
University/education

c/o Clinical Trials Research Unit (CTRU)
University of Leeds
17 Springfield Mount
Leeds
LS2 9NG
England
United Kingdom

"ROR"	https://ror.org/024mrxd33

Funders

Funder type

Research council

Medical Research Council (MRC) (UK)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Plain English results			No	Yes
Interim results article	interim results	01/02/2005	Yes	No
Results article	results on homozygous deletion mapping in myeloma samples	15/03/2010	Yes	No
Results article	results on XBP1s levels in multiple myeloma	15/07/2010	Yes	No
Results article	results on genomic profiling of multiple myeloma	14/10/2010	Yes	No
Results article	results on secondary outcomes	01/08/2011	Yes	No
Results article	results on CTD initial therapy	04/08/2011	Yes	No
Results article	results	01/10/2011	Yes	No
Results article	results and meta-analysis	05/01/2012	Yes	No
Results article	results	01/03/2012	Yes	No
Results article	results	02/08/2012	Yes	No
Results article	results	24/10/2013	Yes	No
Results article	results	01/11/2013	Yes	No
Results article	results	29/05/2014	Yes	No
Results article	results	19/03/2015	Yes	No

Editorial Notes

19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)