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21 March 2013
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| [ Print-friendly version ] |
| MUK six |
| ISRCTN | ISRCTN59395590 |
| DOI | 10.1186/ISRCTN59395590 |
| ClinicalTrials.gov identifier | |
| EudraCT number | 2012-000842-36 |
| Public title | MUK six |
| Scientific title | A Phase I/IIa trial of VTD-panobinostat treatment and panobinostat maintenance in relapsed and relapsed/refractory multiple myeloma patients |
| Acronym | N/A |
| Serial number at source | 13613 |
| Study hypothesis |
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.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13613 |
| Lay summary | Lay summary under review with external organisation |
| Ethics approval | First MREC, 11 July /2012 ref: 12/LO/0965 |
| Study design | Non-randomised interventional study |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Haematological Oncology; Disease: Myeloma |
| Participants - 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 |
| Participants - 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 Investigator’s 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 |
| Anticipated start date | 10/12/2012 |
| Anticipated end date | 01/06/2014 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | UK Sample Size: 54 |
| Interventions |
Dexamethasone, Dexamethasone will be administered for 16 cycles on days 1, 2, 8 and 9
Panobinostat, 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, Thalidomide will be administered daily for 16 cycles Velcade, Velcade will be administered in a regimen alongside panobinostat, thalidomide and dexamethasone |
| Primary outcome measure(s) | Dose limiting toxicities measured within the first cycle of treatment (21 days) |
| Secondary outcome measure(s) | Response - proportion of participants achieving at least a partial response within 16 cycles of VTD-Pano |
| Sources of funding | Myeloma UK |
| Trial website | |
| Publications | |
| Contact name | Mrs Sarah Flynn |
| Address |
University of Leeds
Clinical Trials Research Unit (CTRU) Woodhouse Lane |
| City/town | Leeds |
| Zip/Postcode | LS2 9JT |
| Country | United Kingdom |
| s.flynn@leeds.ac.uk | |
| Sponsor | University of Leeds (UK) |
| Address |
Faculty Research Office
Worsley Building Clarendon Way |
| City/town | Leeds |
| Zip/Postcode | LS2 9NL |
| Country | United Kingdom |
| Sponsor website: | http://www.leeds.ac.uk/ |
| Date applied | 19/12/2012 |
| Last edited | 08/03/2013 |
| Date ISRCTN assigned | 19/12/2012 |
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