Use of Thalidomide, Lenalidomide, Carfilzomib, Bortezomib and Vorinostat in the Initial Treatment of Newly Diagnosed Multiple Myeloma Patients
Myeloma XI
Randomised Comparisons, in Myeloma Patients of All Ages, of Thalidomide, Lenalidomide, Carfilzomib and Bortezomib Induction Combinations, and of Lenalidomide and Combination Lenalidomide Vorinostat as Maintenance (Myeloma XI)
1 other identifier
interventional
4,420
1 country
1
Brief Summary
The purpose of this study is to compare a standard chemotherapy regimen of cyclophosphamide, dexamethasone plus thalidomide with a newer regimen of cyclophosphamide, dexamethasone plus lenalidomide with or without carfilzomib. Patients who do not have the best response to their initial treatment may then also be given a combination of cyclophosphamide, dexamethasone plus bortezomib. Patients who are relatively fit may, on their doctor's advice, go on to receive more intensive chemotherapy, supported with a transplant of their own blood cells. This is standard treatment which patients may be offered anyway even if they didn't take part in this study. After maximal response has been achieved with the treatment described above, and as long as the myeloma has not got worse, patients will be treated with either long-term lenalidomide, lenalidomide with vorinostat, or receive no further treatment, with close observation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-myeloma
Started May 2010
Longer than P75 for phase_3 multiple-myeloma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2010
CompletedFirst Submitted
Initial submission to the registry
February 21, 2012
CompletedFirst Posted
Study publicly available on registry
March 15, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2022
CompletedJune 11, 2018
June 1, 2018
11.6 years
February 21, 2012
June 7, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall survival
Overall survival for induction chemotherapy comparisons is defined as the time from initial randomisation to the trial to death from any cause or last follow-up. Overall survival for maintenance therapy comparisons is defined from the time of maintenance randomisation.
Time from initial randomisation to the trial death from any cause or last follow-up
Progression-free survival
Progression-free survival for induction chemotherapy comparisons is defined as the time from initial randomisation to the trial to progression or death from any cause. Patients who do not progress will be censored at the last date they were known to be alive and progression-free. Progression-free survival for maintenance therapy comparisons is defined from the time of maintenance randomisation
time from initial randomisation to the trial to progression or death from any cause
Secondary Outcomes (2)
Response
Response will be determined according to the modified international uniform response criteria for multiple myeloma
Toxicity
will be based on adverse events as graded by CTCAE v4.0
Study Arms (2)
Intensive pathway
ACTIVE COMPARATORThe intensive pathway is aimed at younger and fitter patients who will receive the standard dose of chemotherapy. The initial treatments will be followed by high-dose chemotherapy with a stem cell transplant which is generally standard practice. Participants receive one treatment from each following stage in intensive pathway, depending on what they are randomised to (Protocol v6.0): 1. Induction treatment: 1. CRD regimen - cyclophosphamide, lenalidomide, dexamethasone 2. CTD regimen - cyclophosphamide, thalidomide, dexamethasone 3. CCRD regimen - carfilzomib, cyclophosphamide, lenalidomide, dexamethasone 2. Consolidation treatment (depending on response to induction treatment): 1. VCD regimen - bortezomib, cyclosphosphamide, dexamethasone 2. No consolidation treatment 3. High-dose therapy and stem cell transplant 4. Maintenance treatment: 1. Lenalidomide maintenance 2. No maintenance 3. Lenalidomide plus vorinostat maintenance (Protocol v5.0 only)
Non-intensive pathway
ACTIVE COMPARATORThe non-intensive pathway is aimed at participants who are not deemed suitable for the stem cell transplant, and will receive lower doses of some of the drugs. Interventions in each stage of non-intensive pathway (depending on what the participant has been randomised to) - from Protocol v6.0: 1. Induction treatment 1. CRDa regimen - cyclophosphamide, lenalidomide, dexamethasone attenuated 2. CTDa regimen - cyclophosphamide, thalidomide, dexamethasone attenuated 2. Consolidation treatment (depending on participant's response to induction treatment): 1. VCD regimen - bortezomib, cyclosphosphamide, dexamethasone 2. No consolidation treatment 3. Maintenance treatment 1. Lenalidomide maintenance 2. No maintenance 3. Lenalidomide plus vorinostat maintenance (\*for participants recruited under Protocol v5.0 only\*)
Interventions
Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4 \& 12-15 - dexamethasone 40 mg daily PO This cycle is repeated every 28 days
Days 1,8,15 (i.e. weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg hard capsules. Initially 100 mg daily PO for 3 weeks, increasing to 200 mg daily PO Days 1-4 and 12-15 - dexamethasone 40 mg daily PO The cycle is repeated every 21 days
Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1 \& 2, 8 \& 9, 15 \& 16 - carfilzomib 20\*/36 mg/m2\*\* IV (\*carfilzomib 20 mg/m2 is only administered on days 1 and 2 of cycle 1; \*\*carfilzomib will be dose capped at a body surface area of 2.2 m2) Days 1-21 - lenalidomide 25 mg daily PO Days 1-4, 8, 9 \& 15, 16 - dexamethasone 40 mg daily PO This cycle is repeated every 28 days
Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4 \& 15-18 - dexamethasone 20 mg daily PO This cycle is repeated every 28 days
Days 1, 8, 15, 22 (weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg hard capsules; initially 50 mg daily PO for 4 weeks, increasing every 4 weeks by 50 mg increments to 200 mg daily PO Days 1-4 \& 15-18 - dexamethasone 20 mg daily PO This cycle is repeated every 28 days
Days 1, 4, 8 \& 11 - bortezomib 1.3 mg/m2 SC or IV Days 1, 8, 15 - cyclophosphamide 500 mg PO Days 1-2, 4-5, 8-9 \& 11-12 - dexamethasone 20 mg daily PO This cycle is repeated every 21 days
Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days
Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 \& 15-21 - vorinostat 300mg PO This cycle is repeated every 28 days
High dose melphalan therapy and autologous stem cell transplant to be given as per local practice
Eligibility Criteria
You may qualify if:
- Aged 18 years or greater
- Newly diagnosed as having symptomatic multiple myeloma or non-secretory multiple myeloma
- Provide written informed consent
- 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
- Women of child bearing potential must have a negative pregnancy test performed by a healthcare professional in accordance with the Celgene-approved process for thalidomide and lenalidomide Risk Management and Pregnancy Prevention
You may not qualify if:
- Asymptomatic myeloma
- Solitary plasmacytoma of bone. (Patients with previous solitary plasmacytoma now progressed to symptomatic or non-secretory myeloma are eligible)
- Extramedullary plasmacytoma (without evidence of myeloma)
- Previous (\<5 years since diagnosis) or concurrent active malignancies, except surgically-removed basal or squamous cell carcinoma of the skin, treated carcinoma in situ of the breast or cervix, or incidental histologic finding of prostate cancer (TMN stage of T1a or 1b). Patients with remote histories (\>5 years) of other cured malignancies may be entered.
- Documented diagnosis of Myelodysplastic Syndrome (MDS) that meets International Prognostic Scoring System (IPSS) criteria for high-risk disease
- Previous treatment for myeloma, except the following: local radiotherapy to relieve bone pain or spinal cord compression; or prior bisphosphonate treatment; or corticosteroids within the last 3 months
- Known history of allergy contributable to compounds containing boron or mannitol
- Grade 2 or greater (NCI criteria) peripheral neuropathy
- Acute renal failure (unresponsive to up to 72 hours of rehydration, characterised by creatinine \>500µmol/L or urine output \<400 mL/day or requirement for dialysis)
- Lactating or breastfeeding
- Patient has active or prior hepatitis C
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Leedslead
- Celgenecollaborator
- Merck Sharp & Dohme LLCcollaborator
- Amgencollaborator
Study Sites (1)
112 sites UK wide
United Kingdom, United Kingdom
Related Publications (4)
Beer SA, Cairns DA, Pawlyn C, Holroyd A, Ferris E, Cook G, Drayson M, Boyd K, Proszek P, Davies FE, de Tute R, Jenner M, Morgan GJ, Owen R, Hubank M, Houlston R, Jackson G, Kaiser MF. Challenging the concept of functional high-risk myeloma through transcriptional and genetic profiling. Blood. 2025 Nov 27;146(22):2670-2680. doi: 10.1182/blood.2025029987.
PMID: 40834881DERIVEDAgbuduwe C, Iqbal G, Cairns D, Menzies T, Dunn J, Gregory W, Kaiser M, Owen R, Pawlyn C, Child JA, Davies F, Morgan GJ, Jackson GH, Drayson MT, Basu S. Clinical characteristics and outcomes of IgD myeloma: experience across UK national trials. Blood Adv. 2022 Sep 13;6(17):5113-5123. doi: 10.1182/bloodadvances.2022007608.
PMID: 35790108DERIVEDde Tute RM, Pawlyn C, Cairns DA, Davies FE, Menzies T, Rawstron A, Jones JR, Hockaday A, Henderson R, Cook G, Drayson MT, Jenner MW, Kaiser MF, Gregory WM, Morgan GJ, Jackson GH, Owen RG. Minimal Residual Disease After Autologous Stem-Cell Transplant for Patients With Myeloma: Prognostic Significance and the Impact of Lenalidomide Maintenance and Molecular Risk. J Clin Oncol. 2022 Sep 1;40(25):2889-2900. doi: 10.1200/JCO.21.02228. Epub 2022 Apr 4.
PMID: 35377708DERIVEDWalker BA, Boyle EM, Wardell CP, Murison A, Begum DB, Dahir NM, Proszek PZ, Johnson DC, Kaiser MF, Melchor L, Aronson LI, Scales M, Pawlyn C, Mirabella F, Jones JR, Brioli A, Mikulasova A, Cairns DA, Gregory WM, Quartilho A, Drayson MT, Russell N, Cook G, Jackson GH, Leleu X, Davies FE, Morgan GJ. Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma. J Clin Oncol. 2015 Nov 20;33(33):3911-20. doi: 10.1200/JCO.2014.59.1503. Epub 2015 Aug 17.
PMID: 26282654DERIVED
Related Links
- The ISRCTN register has further information about the Myeloma XI trial. Click on the link above for further information about the trial
- ASCO 2017 abstract: Lenalidomide induction and maintenance therapy for transplant eligible myeloma patients: Results of the Myeloma XI study
- EHA 2017 abstract: QUADRUPLET VS SEQUENTIAL TRIPLET INDUCTION THERAPY FOR MYELOMA PATIENTS: RESULTS OF THE MYELOMA XI STUDY. (EHA-3097)
- EHA 2017 abstract: LENALIDOMIDE INDUCTION AND MAINTENANCE THERAPY FOR TRANSPLANT ELIGIBLE MYELOMA: PATIENTS: RESULTS OF THE MYELOMA XI STUDY (EHA-1279)
- Paper in Blood Cancer Journal: Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Graham Jackson
Freeman Health System
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 21, 2012
First Posted
March 15, 2012
Study Start
May 1, 2010
Primary Completion
December 1, 2021
Study Completion
December 1, 2022
Last Updated
June 11, 2018
Record last verified: 2018-06