MUK six

ISRCTN	ISRCTN59395590
DOI	https://doi.org/10.1186/ISRCTN59395590
EudraCT/CTIS number	2012-000842-36
Secondary identifying numbers	13613

Submission date: 19/12/2012
Registration date: 19/12/2012
Last edited: 21/05/2021

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 of protocol

http://www.cancerresearchuk.org/cancer-help/trials/a-trial-of-panobinostat-with-bortezomib-thalidomide-and-dexamethasone-for-myeloma-that-has-come-back-or-no-longer-responding-to-treatment-muk-six

Contact information

Mrs Sarah Flynn
Scientific

University of Leeds
Clinical Trials Research Unit (CTRU)
Woodhouse Lane
Leeds
LS2 9JT
United Kingdom

Email	s.flynn@leeds.ac.uk

Study information

Study design	Non-randomised interventional study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	A Phase I/IIa trial of VTD-panobinostat treatment and panobinostat maintenance in relapsed and relapsed/refractory multiple myeloma patients
Study objectives	This is an open label, multi-centre, phase I/IIa trial to firstly identify the maximum tolerated dose (MTD) of VTD-panobinostat in eligible participants with relapsed or relapsed and refractory multiple myeloma. A rolling six dose escalation design36 is proposed to determine the MTD and recommended dose (RD) of VTD-Pano. An expansion phase will then be incorporated to estimate the response rate (partial response or better) within 16 cycles of therapy at the RD. Safety will be assessed throughout the trial.
Ethics approval(s)	First MREC, 11/07/2012, ref: 12/LO/0965
Health condition(s) or problem(s) studied	Haematological Oncology; Disease: Myeloma
Intervention	Dexamethasone will be administered for 16 cycles on days 1, 2, 8 and 9 Panobinostat will be administered alongside Velcade, Thalidomide and Dexamethasone for 16 cycles of induction therapy, each lasting 21 days. Participants will then receive 12 months of panobinostat monotherapy maintenance. Thalidomide will be administered daily for 16 cycles Velcade will be administered in a regimen alongside panobinostat, thalidomide and dexamethasone
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	Dexamethasone, panobinostat, thalidomide, velcade
Primary outcome measure	Dose limiting toxicities measured within the first cycle of treatment (21 days)
Secondary outcome measures	Response - proportion of participants achieving at least a partial response within 16 cycles of VTD-Pano
Overall study start date	10/12/2012
Completion date	01/06/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	UK Sample Size: 54
Key inclusion criteria	1. Patients with a previous diagnosis of multiple myeloma based on IMWG 2003 definitions: 1.1. Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation of serum or of total 24 hour urine 1.2. Bone marrow (clonal) plasma cells =10% or biopsy proven plasmacytoma 1.3. Related organ or tissue impairment (CRAB symptoms, anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections) 2. Relapsed or relapsed-and-refractory myeloma who have received 14 prior lines and now require further treatment 3. Able to give informed consent and willing to follow study protocol 4. Aged 18 years or over 5. ECOG Performance Status = 2 6. Required laboratory values within 14 days of registration: 6.1. Absolute neutrophil count = 1.0 x 109/L. Growth factor support is not permitted within 14 days prior to eligibility assessment 6.2. Platelet count = 100 x 109/L. Platelet support is not permitted within 14 days prior to eligibility assessment 6.3. Haemoglobin = 8.0g/dL. Blood transfusion support is permitted 6.4. Bilirubin = 2 x upper limit of normal (ULN) 6.5. AST and/or ALT = 2.5 x ULN; except in subjects with known hepatic involvement, where AST and/or ALT = 5.0 x ULN 6.6. Serum creatinine = 2.0 x ULN 6.7. Corrected calcium = 2.8 mmol/L 7. Anticipated survival of at least 3 months 8. Evaluable disease per modified IWG criteria, utilising the following assessments as appropriate: 8.1. Serum M protein = 10g/l 8.2. Urine M protein = 200mg/24 hours 8.3. Serum free light chain assay: involved FLC level = 100mg/l. Provided serum FLC ratio is abnormal 9. Female subjects of childbearing potential must have a negative pregnancy test at baseline and agree to use dual methods of contraception for the duration of the study and must continue to do so for 3 months after the end of treatment. Male subjects must agree to use a barrier method of contraception for the duration of the study if sexually active with a female of childbearing potential and must continue to do so for 3 months after the end of treatment. 10. Male or female participants
Key exclusion criteria	1. Pregnant (positive pregnancy test) or breastfeeding women 2. Non-secretory multiple myeloma 3. Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 28 days before the start of protocol treatment. Steroid therapy is permitted (maximum 160mg dexamethasone or equivalent), but must be stopped 48 hours prior to study drug administration. Bisphosphonates for bone disease and radiotherapy for palliative intent are also permitted. 4. Concurrent or previous malignancies (<12 months post end of treatment) at other sites with the exception of appropriately treated localised epithelial skin or cervical cancer, or incidental histologic findings of prostate cancer (TMN stage T1a or 1b). Patients with histories (=12 months) of other tumours may be entered 5. Poorly controlled or serious medical or psychiatric illness that, in the Investigators opinion, is likely to interfere with participation and/or compliance in this clinical study 6. Patients with significant cardiovascular disease (e.g. history of congestive heart failure requiring therapy, presence of severe valvular heart disease, presence of an atrial or ventricular arrhythmia requiring treatment, uncontrolled hypertension, a history of QTc abnormalities) 7. Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis 8. Gastrointestinal disorders that may interfere with absorption of the study drug 9. Patients who have been refractory to prior bortezomib, i.e. did not achieve at least an MR, or who have progressed on therapy or within 60 days of last dose 10. Participants with peripheral neuropathy CTC grade 2 or higher or grade 1 with pain within 14 days prior to registration 11. Any history of known hypersensitivity to any of the study medication or excipients
Date of first enrolment	10/12/2012
Date of final enrolment	01/06/2014

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University of Leeds

Leeds
LS2 9JT
United Kingdom

Sponsor information

University of Leeds (UK)
University/education

Faculty Research Office
Worsley Building
Clarendon Way
Leeds
LS2 9NL
England
United Kingdom

Website	http://www.leeds.ac.uk/
"ROR"	https://ror.org/024mrxd33

Funders

Funder type

Charity

Myeloma UK
Private sector organisation / Other non-profit organizations

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	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	01/12/2016		Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

21/05/2021: Cancer Research UK lay results summary link added to Results (plain English).
16/11/2016: Publication reference added.