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 a positive decision, giving patients previously treated with lenalidomide and bortezomib access to pomalidomide and dexamethasone.
Funded by Napp Pharmaceuticals
Publication(s):
- 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.
- 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):
- 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 the 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):
- 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
- 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
- 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. 23rd Annual Meeting of the European Haematological Association. Abstracts PF554
- 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
- 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.
- 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 trial 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):
- 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.
- 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.
- 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
- 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.