Multiple MyelomaPhase 3Myeloma XINCT01554852
Use of Thalidomide, Lenalidomide, Carfilzomib, Bortezomib and Vorinostat in the Initial Treatment of Newly Diagnosed Multiple Myeloma Patients
A Phase 3 study testing Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen, Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen and Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen in people with Multiple Myeloma, run by University of Leeds at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen, Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen and Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,420 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2010to Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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)
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.
Read more
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.
Read the detailed description
The last ten years has seen the introduction of a number of effective new anti-myeloma agents into the clinical arena. These agents have been shown to be highly effective in the relapse setting and now are being introduced as treatment earlier in the disease course.
This study aims to address in the randomised setting some of the key questions concerning the use of thalidomide, bortezomib, lenalidomide, carfilzomib and vorinostat in the initial treatment of multiple myeloma patients.
Newly diagnosed patients of all ages with symptomatic myeloma requiring treatment are eligible.
For initial treatment, thalidomide in combination with cyclophosphamide and dexamethasone, the UK gold standard, will be compared with the newer combination of lenalidomide, cyclophosphamide and dexamethasone with or without carfilzomib.
For patients with a sub-optimal response to initial therapy, the response to the proteasome inhibitor bortezomib will be assessed, as previous studies have demonstrated that it is able to induce responses and improve progression-free and overall survival in patients resistant to standard chemotherapy. Patients young and fit enough to tolerate an autologous transplant will then proceed to high dose melphalan with peripheral blood stem cell rescue and then on to maintenance randomisation. Older or less fit patients will go directly to a maintenance randomisation.
The value of lenalidomide and lenalidomide combined with vorinostat maintenance will then be assessed by randomising eligible patients to receive either lenalidomide, lenalidomide combined with vorinostat maintenance therapy, or close observation.
The primary end points of the study are overall and progression-free survival (OS and PFS). Secondary end points include response and toxicity.
A number of laboratory based studies will also be performed in order to determine patient specific factors predicting overall and progression-free survival and response to treatment.
- Conditions
- Multiple Myeloma
- Being tested
- Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen, Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen, Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen, Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimen, Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimen
- Keywords
- myeloma, lenalidomide, Revlimid, cyclophosphamide, dexamethasone, bortezomib, Velcade, vorinostat, Zolinza, stem cell, carfilzomib, Kyprolis
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimenDrug
Also called Revlimid (lenalidomide)
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
Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimenDrug
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
Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimenDrug
Also called Kyprolis (carfilzomib), Revlimid (lenalidomide)
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
Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimenDrug
Also called Revlimid (lenalidomide)
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
Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimenDrug
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
Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimenDrug
Also called Velcade (bortezomib)
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
Maintenance (intensive & non-intensive pathways) - lenalidomide maintenanceDrug
Also called Revlimid (lenalidomide)
Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days
Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenanceDrug
Also called Revlimid (lenalidomide), Zolinza (vorinostat)
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 (intensive pathway only)Drug
High dose melphalan therapy and autologous stem cell transplant to be given as per local practice
| Study group | Role | What they receive |
|---|---|---|
| Intensive pathway | Active comparator | The 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) Receives: Drug: Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen; Drug: Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen; Drug: Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen; Drug: Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen; Drug: Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance; Drug: Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance; Drug: High dose melphalan therapy and autologous stem cell transplant (intensive pathway only) |
| Non-intensive pathway | Active comparator | The 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*) Receives: Drug: Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimen; Drug: Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimen; Drug: Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen; Drug: Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance; Drug: Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: time from initial randomisation to the trial to progression or death from any cause
Secondary outcomes (2)
Response
Disease progression and response rates will be determined according to the modified International uniform response criteria for multiple myeloma
Measured: Response will be determined according to the modified international uniform response criteria for multiple myeloma
Toxicity
Toxicity will be reported based on adverse events, as graded by CTCAE V4.0 and determined by routine clinical assessments at each centre
Measured: will be based on adverse events as graded by CTCAE v4.0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2012 (estimated)
- Study startMay 2010
- Primary completionDec 2021 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4,420 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene, Merck Sharp & Dohme LLC, Amgen
- Responsible party
- Sponsor
- Investigators
- Graham Jackson, Principal investigator, Freeman Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01554852
- Sponsor's protocol ID
- EudraCT number: 2009-010956-93
- Acronym
- Myeloma XI
- Status last verified
- Jun 2018
- First submitted
- 21 Feb 2012
- Last updated
- 11 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 40834881Agbuduwe 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.
PubMed 35790108de 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.
PubMed 35377708Walker 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.
PubMed 26282654
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01554852
- Acronym / sponsor ID
- Myeloma XI / EudraCT number: 2009-010956-93
- Conditions
- Multiple Myeloma
- Keywords
- myeloma, lenalidomide, Revlimid, cyclophosphamide, dexamethasone, bortezomib, Velcade, vorinostat
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4,420 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- Celgene, Merck Sharp & Dohme LLC, Amgen
- Study start
- May 2010
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 15 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The last ten years has seen the introduction of a number of effective new anti-myeloma agents into the clinical arena. These agents have been shown to be highly effective in the relapse setting and now are being introduced as treatment earlier in the disease course.
This study aims to address in the randomised setting some of the key questions concerning the use of thalidomide, bortezomib, lenalidomide, carfilzomib and vorinostat in the initial treatment of multiple myeloma patients.
Newly diagnosed patients of all ages with symptomatic myeloma requiring treatment are eligible.
For initial treatment, thalidomide in combination with cyclophosphamide and dexamethasone, the UK gold standard, will be compared with the newer combination of lenalidomide, cyclophosphamide and dexamethasone with or without carfilzomib.
For patients with a sub-optimal response to initial therapy, the response to the proteasome inhibitor bortezomib will be assessed, as previous studies have demonstrated that it is able to induce responses and improve progression-free and overall survival in patients resistant to standard chemotherapy. Patients young and fit enough to tolerate an autologous transplant will then proceed to high dose melphalan with peripheral blood stem cell rescue and then on to maintenance randomisation. Older or less fit patients will go directly to a maintenance randomisation.
The value of lenalidomide and lenalidomide combined with vorinostat maintenance will then be assessed by randomising eligible patients to receive either lenalidomide, lenalidomide combined with vorinostat maintenance therapy, or close observation.
The primary end points of the study are overall and progression-free survival (OS and PFS). Secondary end points include response and toxicity.
A number of laboratory based studies will also be performed in order to determine patient specific factors predicting overall and progression-free survival and response to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intensive pathway | Active comparator | Drug: Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen, Drug: Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen, Drug: Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen, Drug: Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen, Drug: Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance, Drug: Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance, Drug: High dose melphalan therapy and autologous stem cell transplant (intensive pathway only)The 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 comparator | Drug: Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimen, Drug: Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimen, Drug: Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen, Drug: Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance, Drug: Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenanceThe 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*) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimenAlso: Revlimid (lenalidomide)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 | Drug | Intensive pathway |
| Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimenDays 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 | Drug | Intensive pathway |
| Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimenAlso: Kyprolis (carfilzomib), Revlimid (lenalidomide)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 | Drug | Intensive pathway |
| Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimenAlso: Revlimid (lenalidomide)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 | Drug | Non-intensive pathway |
| Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimenDays 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 | Drug | Non-intensive pathway |
| Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimenAlso: Velcade (bortezomib)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 | Drug | Intensive pathway, Non-intensive pathway |
| Maintenance (intensive & non-intensive pathways) - lenalidomide maintenanceAlso: Revlimid (lenalidomide)Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days | Drug | Intensive pathway, Non-intensive pathway |
| Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenanceAlso: Revlimid (lenalidomide), Zolinza (vorinostat)Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 \& 15-21 - vorinostat 300mg PO This cycle is repeated every 28 days | Drug | Intensive pathway, Non-intensive pathway |
| High dose melphalan therapy and autologous stem cell transplant (intensive pathway only)High dose melphalan therapy and autologous stem cell transplant to be given as per local practice | Drug | Intensive pathway |
Primary outcome
Overall survival
Time frame: Time from initial randomisation to the trial death from any cause or last follow-up
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.
Progression-free survival
Time frame: time from initial randomisation to the trial to progression or death from any cause
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
2 secondary outcomes
Response
Time frame: Response will be determined according to the modified international uniform response criteria for multiple myeloma
Toxicity
Time frame: will be based on adverse events as graded by CTCAE v4.0
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2018.
- Derived from this study: PubMed 40834881Beer 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.
- Derived from this study: PubMed 35790108Agbuduwe 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.
- Derived from this study: PubMed 35377708de 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.
- Derived from this study: PubMed 26282654Walker 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.
- The ISRCTN register has further information about the Myeloma XI trial. Click on the link above for further information about the trialLink provided by the sponsor.
- Cancer research UK provides helpful information about the intensive arm of the trial. Click here for more information.Link provided by the sponsor.
- Cancer research UK provides helpful information about the non-intensive arm of the trial. Click here for more informationLink provided by the sponsor.
- ASCO 2017 abstract: Lenalidomide induction and maintenance therapy for transplant eligible myeloma patients: Results of the Myeloma XI studyLink provided by the sponsor.
- EHA 2017 abstract: QUADRUPLET VS SEQUENTIAL TRIPLET INDUCTION THERAPY FOR MYELOMA PATIENTS: RESULTS OF THE MYELOMA XI STUDY. (EHA-3097)Link provided by the sponsor.
- EHA 2017 abstract: LENALIDOMIDE INDUCTION AND MAINTENANCE THERAPY FOR TRANSPLANT ELIGIBLE MYELOMA: PATIENTS: RESULTS OF THE MYELOMA XI STUDY (EHA-1279)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Graham Jackson principal investigator
Freeman Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen, Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen and Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen in people with Multiple Myeloma, run by University of Leeds at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: Time from initial randomisation to the trial death from any cause or last follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01554852, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2018.