Myeloma UK Clinical Trials

On-going trials – Open to recruitment

MUK twelve

A Phase 2 trial evaluating the safety and efficacy of selinexor in combination with cyclophosphamide and prednisolone versus cyclophosphamide and prednisolone in relapsed/refractory myeloma patients.

This trial aims to show that addition of selinexor to cyclophosphamide and prednisolone improves progression free survival in relapsed/refractory patients.

What this means for patients

The results from this trial will increase the evidence for the use of selinexor in combination with cyclophosphamide and prednisolone in relapsed/refractory patients.

Trial delivery funded by Karyopharm

MUK nine

A Phase 2 trial with two parts. This trial aims to find out if a multi-targeted combination of five drugs could improve outcomes in high risk myeloma patients.

In first part, MUK nine a, over 700 newly diagnosed patients will be screened using genetic analysis of their bone marrow samples. Those patients who are identified as being at high-risk will be offered the opportunity to take part in MUK nine b.

In the second part, MUK nine b, patients defined as high-risk in MUK nine a will be given a combination of bortezomib (Velcade®), lenalidomide (Revlimid®) dexamethasone, daratumumab (Darzalex®) with cyclophosphamide as induction treatment prior to high dose therapy and stem cell transplant. Patients will then receive consolidation (daratumuab, bortezomib and lenalidomide) and maintenance (daratumuab and lenalidomide) treatments.

What this means for patients

The results from this trial will give a greater understanding of how to treat high risk myeloma patients. It will also help demonstrate how genetic screening from patient bone marrow can be used to group and treat certain myeloma patients (known as stratified medicine).

Funded by Celgene and Janssen

Publication(s):

1. Shah, V., Hinsley , S., Sherborne, A., Ellis, S., Price, A. , Kendall, J., Johnson, D., Owen, R., Drayson, M., Flanagan, L., Sherratt, D., Gregory, W., Jackson, G., Pratt, G., Cook, G., Brown, S., Jenner, M., Kaiser, M. (2018) Optimising treatment for high-risk myeloma in a stratified multicentre trail: experience from the MUK nine Optimum study. 23^rd Annual Meeting of the European Haematological Association. Abstract PS1334
2. Sherborne, A.L., Shah, V., Ellis, S., Begum, F., Kendall, J., Johnson, D.C., Owen, R.G., Drayson, M.T., Flanagan, L., Sherratt, D. and Gregory, W.M., (2017). Improving Outcomes for Patients with High-Risk Myeloma Via Prospective Trial Evidence: The Myeloma UK Nine Optimum Trial. 130: (Suppl. 1), 1767.

On-going trials – Closed to recruitment

MUK seven

A randomised Phase 2 trial comparing pomalidomide (Inovid ®), cyclophosphamide and dexamethasone (CPD) to pomalidomide and dexamethasone (PD) in relapsed/refractory myeloma patients.

This trial aims to show that CPD is comparable or better than PD. The trial will also screen patient samples to look for biomarkers (e.g. differences in genetics or immune cell composition) which correlate with lower responses to pomalidomide to help predict patient response to pomalidomide.

What this means for patients

Preliminary results from this trial showed that CPD significantly increases response rates and depth of response compared to pomalidomide and dexamethasone in relapsed/refractory patients. These results increase the evidence for CPD as a treatment for relapsed/refractory patients.

Funded by Celgene and Myeloma UK

Publication(s):

1. Croft, J., Hall, A., Walker, K., Sherborne, A.L., Ellis, S., Price, A., Sherratt, D., Reed, S., Pawlyn, C., Garg, M. and Boyd, K., (2018). Cyclophosphamide, Pomalidomide and Dexamethasone Significantly Improves Response over Poma/Dex in Relapsed/Refractory Myeloma Patients Previously Treated with Cyclophosphamide Combination Therapy-Initial Results of the Randomised Multicentre Mukseven Trial. 132:(Suppl. 1), 3274
2. Croft, J., Hall, A., Walker, K., Sherborne, A.L., Boyd, K., Garg, M., Pawlyn, C., Sherratt, D., Reed, S., Pierceall, W.E. and Cook, G., (2018). Cyclophosphamide Exerts Significant Immunomodulatory Function in Myeloma Patients Treated with Pomalidomide and Dexamethasone. 132:(Suppl. 1), 4482
3. Sherborne, A.L., Shah, V., Hall, A., Walker, K., Ellis, S., Begum, F., Johnson, D.C., Croft, J., Kendall, J., Pawlyn, C. and Atanesyan, L., (2017). Molecular Profiling of Relapsed and Refractory Myeloma Identifies Frequent Bi-Allelic Driver Events—Interim Results of the’Myeloma UK Seven’Biomarker Trial. 130:(Suppl. 1), 1851.

MUK eight

A randomised Phase 2 trial comparing a combination of ixazomib (Ninlaro®) with cyclophosphamide and dexamethasone (ICD) against cyclophosphamide and dexamethasone (CD) in relapsed/refractory myeloma patients.

This trial aims to show that ICD is comparable to or better than CD, delivering improved response rates in relapsed/refractory patients.

What this means for patients

The results from this trial will increase the evidence for ICD in relapsed/refractory patients.

Funded by Takeda and Myeloma UK

MUK eleven

A Phase 1 trial to assess the safety and efficacy of Reolysin®, a reovirus, in combination with lenalidomide and pomalidomide in relapsed/refractory myeloma patients.

This trial is the first human trial assessing the efficacy and safety of Reolysin in combination with lenalidomide and pomalidomide. It aims to identify the most effective dose of Reolysin and show that it is well tolerated.

What this means for patients

These result will provide further evidence towards the use of viruses to treat myeloma. There are currently no viral treatments licenced to treat myeloma therefore this work could help to find a way to kill myeloma cells.

Funded by Celgene and Myeloma UK

Completed Trials

MUK one

A Phase 2 trial identifying the optimal dose of bendamustine when given in combination with thalidomide and dexamethasone in relapsed/refractory myeloma patients.

What this means for patients

This study demonstrated that bendamustine with thalidomide and dexamethasone was effective and well tolerated in relapsed/refractory myeloma patients.

Data from this trial was used to help demonstrate the clinical benefit of pomalidomide with dexamethasone in relapsed/refractory myeloma patients in a National Institute for Health and Care Excellence (NICE) appraisal. This resulted in positive decision, giving patients previously treated with lenalidomide and bortezomib access to pomalidomide and dexamethasone.

Funded by Napp Pharmaceuticals

Publication(s):

1. Schey, S., Brown, S.R., Tillotson, A.L., Yong, K., Williams, C., Davies, F., Morgan, G., Cavenagh, J., Cook, G., Cook, M. and Orti, G., (2015). Bendamustine, thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUK one randomized dose selection trial. British journal of haematology, 170(3), pp.336-348.
2. Yong, K.L., Williams, C.D., Davies, F.E., Morgan, G.J., Cavenagh, J.D., Cook, G., Cook, M., Coney, A.L., Brown, S., Flanagan, L.M. and Gregory, W., (2013). Identifying an optimally effective but tolerable dose of bendamustine in combination with thalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. 122(21): 286

MUK three

A Phase 1/2a trial identifying the optimal dose of CHR-3996 (a histone deacetylase inhibitor like panobinostat) in combination with tosedostat for relapsed/refractory myeloma patients.

What this means for patients

This study evaluated the safety effectiveness and of two new drugs CHR-3996 and tosedostat as potential new treatments for myeloma.

This study showed that the combination of CHR-3996 and tosedostat was safe and tolerable in multiply relapsed, refractory myeloma patients. This provides further evidence to support the use of histone deacetylase inhibitors to treat myeloma.

Funded by Chroma Therapeutics

Publication(s):

1. Popat, R., Brown, S.R., Tillotson, A.L., Collinson, F., Flanagan, L.M., Williams, C.D., Yong, K.L., Cook, G., Jenner, M.W., Kaiser, M. and Cavet, J., (2016). A Phase I Dose-Escalation Study of the Class 1 Selective Histone Deacetylase Inhibitor CHR-3996 in Combination with Tosedostat for Patients with Relapsed, Refractory Multiple Myeloma: Results of the Muk Three Trial. 128:(Suppl. 1), 3321

MUK four

A Phase 2 trial assessing the safety and effectiveness of vorinostat, (a histone deacetylase (HDAC) inhibitor like panobinostat), in combination with bortezomib and dexamethasone (VVD) in relapsed and/or relapsed refractory myeloma patients.

What this means for patients

This trial showed that vorinostat in combination with bortezomib and dexamethasone was effective and well tolerated. It demonstrated that the combination of proteasome inhibitor, HDAC inhibitor and dexamethasone offers promise for the treatment of relapsed and refractory myeloma patients.

Funded by Merck Sharp & Dohme and Myeloma UK

Publication(s):

Jenner, M.W., Tillotson, A.L., Brown, S.R., Flanagan, L.M., Sherratt, D., Pawlyn, C., Williams, C. and Davies, F.E., (2015). Velcade, Vorinostat and Dexamethasone (V2 D) in Relapsed Myeloma: Results of the Phase 2 Muk Four Trial.  Blood. 126(23): 1852

MUK five

A Phase 2 trial comparing the safety and effectiveness of carfilzomib (Kyprolis®), cyclophosphamide and dexamethasone (KCD) versus cyclophosphamide, bortezomib and dexamethasone (CVD) for myeloma patients at first relapse. It will also evaluate the benefit of cafilzomib maintenance versus observation in patients receiving KCD.

Results from the trial have shown KCD achieved a higher overall response to treatment and lead to deeper responses in high risk myeloma patients than CVD. It also demonstrated that carfilzomib maintenance is well tolerated, improved progression free survival and increased the size of response to treatment.

What this means for patients

This trial has increased the evidence for using carfilzomib, cyclophosphamide and dexamethasone (KCD) instead of cyclophosphamide, bortezomib and dexamethasone (CVD) for patients at their first relapse. It has also demonstrated the benefit of using proteasome inhibitors as maintenance treatments.

Funded by Amgen and Myeloma UK 

Publication(s):

1. Yong, K., Hinsley, S., De Tute, R.M., Sherratt, D., Brown, S.R., Flanagan, L., Williams, C., Cavenagh, J., Kaiser, M., Rabin, N.K. and Ramasamy, K., (2018). Maintenance with Carfilzomib Following Carfilzomib, Cyclophosphamide and Dexamethasone at First Relapse or Primary Refractory Multiple Myeloma (MM) on the Phase 2 Muk Five Study: Effect on Minimal Residual Disease. 132(Suppl. 1): 802
2. Yong, K., Hinsley, S., Sherratt, D., Kendall, J., Brown, S.R., Flanagan, L., Williams, C., Cavenagh, J., Kaiser, M., Rabin, N.K. and Ramasamy, K., (2018). Carfilzomib Versus Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): Outcomes Based on Genetic Risk and Long Term Follow up of the Phase 2 Muk Five Study. 132(Suppl. 1): 306
3. Yong, K., Hinsley, S., Sherratt, D., Brown, S.R., Flanagan, L., Williams, C., Cavenagh, J., Kaiser, M., Rabin, N.K., Ramasamy, K., Garg, M., Auner, H., Hawkins, S. , Bygrave, C., De Tute, R. , Morgan, G., Davies, F., Owen, R., (2018) Single agent carfilzomib prolongs PFS following triplet therapy with cyclophosphamide & dexamethasone for first relapse/primary refractory multiple myeloma: Phase 2 MUK five study, second analysis. 23^rd Annual Meeting of the European Haematological Association. Abstracts PF554
4. Yong, K., Hinsley, S., Auner, H.W., Sherratt, D., De Tute, R.M., Brown, S., Flanagan, L., Williams, C., Cavenagh, J., Kaiser, M.F. and Rabin, N., (2017). Carfilzomib, cyclophosphamide and dexamethasone (KCD) versus bortezomib, cyclophosphamide and dexamethasone (VCD) for treatment of first relapse or primary refractory multiple myeloma (MM): first final analysis of the phase 2 Muk Five study. 130 (Suppl. 1): 835
5. Brown, S., Hinsley, S., Ballesteros, M., Bourne, S., McGarry, P., Sherratt, D., Flanagan, L., Gregory, W., Cavenagh, J., Owen, R. and Williams, C., (2016) The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma. BMC hematology, 16(1), 14.
6. Yong, K.L., Brown, S., Hinsley, S., Flanagan, L., Rabin, N., Ramasamy, K., Cavenagh, J., Owen, R.G., Kaiser, M.F., Low, E. and Williams, C., (2015) Carfilzomib, cyclophosphamide and dexamethasone is well tolerated in patients with relapsed/refractory multiple myeloma who have received one prior regimen. 126(23): 1804

MUK six

A Phase 1/2a trial to identify the optimum dose and evaluate the efficacy and safety of a combination panobinostat, bortezomib, thalidomide and dexamethasone (pano-VTD) in relapsed/refractory myeloma patients. It also evaluated the safety and efficacy of panobinostat maintenance.

Results from this trail demonstrated that panobinostat in combination with bortezomib, thalidomide, and dexamethasone is well tolerated and effective for patients with relapsed multiple myeloma. It also suggested that maintenance with panobinostat had limited effectiveness but was well tolerated.

What this means for patients

This study increased the evidence for using the drug panobinostat with bortezomib, thalidomide, and dexamethasone in relapsed/refractory myeloma patients.

Funded by Novartis and Myeloma UK

Publication(s):

1. Popat, R., Brown, S.R., Flanagan, L., Hall, A., Gregory, W., Kishore, B., Streetly, M., Oakervee, H., Yong, K., Cook, G. and Low, E., 2018. Extended follow-up and the feasibility of Panobinostat maintenance for patients with Relapsed Multiple Myeloma treated with Bortezomib, Thalidomide, Dexamethasone plus Panobinostat (MUK six open label, multi-centre phase I/II Clinical Trial).British journal of haematology.
2. Popat, R., Brown, S.R., Flanagan, L., Hall, A., Gregory, W., Kishore, B., Streetly, M., Oakervee, H., Yong, K., Cook, G. and Low, E., 2016. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial. The Lancet Haematology, 3(12), e572-e580.
3. Popat, R., Brown, S.R., Flanagan, L.M., Hall, A., Kishore, B., Streetly, M., Oakervee, H.E., Hallam, S.L., Smith, M., Yong, K.L. and Cook, G., (2015). Bortezomib (Velcade), thalidomide, dexamethasone and panobinostat (VTD-P) is a safe, well tolerated and efficacious regimen for patients with relapsed multiple myeloma: preliminary results of the Muk-Six trial. 126(23): 1826
4. Popat, R., Brown, S., Flanagan, L. M., Cavenagh, J. D. (2014). Velcade, thalidomide, dexamethasone and panobinostat (VTD-P) for patients with relapsed and relapsed/refractory myeloma: preliminary results of the Muk-Six phase I/IIa trial. 124(21): 4766.

You can learn more about myeloma clinical trials currently recruiting in the UK via our trial finder page.

You can also find out about emerging treatments by reading our Horizons Infosheets or find out where a specific drug is in the clinical trial pathway, by using our drug finder tool.

Last updated Feb 2019.