Multiple MyelomaPhase 1/2MUKsixNCT02145715
Velcade, Thalidomide, Dexamethasone and Panobinostat Treatment and Panobinostat Maintenance in Multiple Myeloma
A Phase 1/2 study testing Velcade, Thalidomide and Dexamethasone in people with Multiple Myeloma, run by Prof Jamie Cavenagh at 5 sites in United Kingdom.
Trial summary
Velcade (bortezomib), thalidomide and dexamethasone (VTD) has been demonstrated to be a highly effective combination in both patients with previously untreated and those with relapsed multiple myeloma. 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?
- Velcade, Thalidomide and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Jan 2013to Jan 2016
- Phase
- Phase 1/2
- 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
- Patients with a previous diagnosis of multiple myeloma based on IMWG 2003 definitions:
- Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation of serum or of total 24 hour urine
- Bone marrow (clonal) plasma cells ≥ 10% or biopsy proven plasmacytoma
- Related organ or tissue impairment (CRAB symptoms, anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections)
- Relapsed and relapsed-and-refractory myeloma who have received 1-4 prior lines and now require further treatment
- Able to give informed consent and willing to follow study protocol
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- Aged 18 years or over
- ECOG Performance Status ≤2
- Required laboratory values within 14 days of registration:
- Absolute neutrophil count ≥1.0 x 109/L.
- Platelet count ≥100 x 109/L.
- Haemoglobin ≥8.0g/dL.
- Bilirubin ≤2 upper limit of normal (ULN)
- AST and/or ALT ≤2.5 ULN; except in subjects with known hepatic involvement, where AST and/or ALT ≤5.0 ULN
- Serum creatinine ≤2.0 ULN
- Corrected calcium ≤2.8 mmol/L.
- Anticipated survival of at least 3 months
- Evaluable disease per modified IWG criteria, utilising the following assessments as appropriate:
- Serum M protein ≥ 10g/l.
- Urine M protein ≥ 200mg/24 hours
- Serum free light chain assay: involved FLC level ≥ 100mg/l. Provided serum FLC ratio is abnormal
- Female subjects of child-bearing 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 child-bearing potential and must continue to do so for 3 months after the end of treatment.
Who cannot join
- Pregnant (positive pregnancy test) or breastfeeding women.
- Non-secretory Multiple Myeloma 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 160 mg 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.
- 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.
- 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
- 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 clinically significant QTc abnormalities)
- Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis.
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- Gastrointestinal disorders that may interfere with absorption of the study drug
- 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
- Participants with peripheral neuropathy CTC grade 2 or higher or grade 1 with pain within 14 days prior to registration
- Any history or known hypersensitivity to any of the study medications or excipients
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
Birmingham Heartlands Hospital
Birmingham, UK, B9 5SS
Royal Liverpool University Hospital
Liverpool, L7 8XP
St Bartholomew's Hospital
London, EC1A 7BE
University College London Hospitals NHS Foundation Trust
London, WC1E 6AG
Guy's Hospital
London
About this study
Official title: A Phase I/IIa Trial of VTD-panobinostat Treatment and Panobinostat Maintenance in Relapsed and Relapsed/Refractory Multiple Myeloma Patients
Velcade (bortezomib), thalidomide and dexamethasone (VTD) has been demonstrated to be a highly effective combination in both patients with previously untreated and those with relapsed multiple myeloma. In previously untreated patients VTD demonstrated clear superiority to TD as induction therapy prior to planned tandem autologous stem cell transplant.
The rationale of this trial is to combine a 'gold standard' antiMM combination with the HDAC inhibitor Panobinostat. There is emerging data to support the concept of clinical synergy between BTZ and HDACi's.
The purpose of this study is to determine the maximum tolerated dose (MTD) and estimated response rates of panobinostat, administered in combination with VTD, in subjects with relapsed and relapsed/refractory multiple myeloma.
- Conditions
- Multiple Myeloma
- Being tested
- Velcade, Thalidomide, Dexamethasone, Panobinostat
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VelcadeDrug
Also called Bortezomib
ThalidomideDrug
DexamethasoneDrug
PanobinostatDrug
| Study group | Role | What they receive |
|---|---|---|
| Velcade, Thalidomide, Dexamethasone (VTD) + Panobinostat | Experimental | Up to 16 cycles of VTD+Panobinostat followed by panobinostat maintenance for 1 year or until disease progression.
* Induction - Cycles 1-16 (21-day cycle)
* Velcade: 1.3mg/m2 (subcutaneous) on days 1 and 8
* Thalidomide: 100mg (PO)on days 1 -21
* Dexamethasone: 20 mg (PO) on days 1, 2, 8 and 9
* Panobinostat: 10mg, 15mg or 20mg days 1, 3, 5, 8, 10 and 12 Dose depends on cohort entry at registration during the dose escalation phase. The recommended dose will be used during the expansion phase.
* Panobinostat monotherapy maintenance for 1 year. Panobinostat will be given at the same dose as the recommended dose during expansion phase Receives: Drug: Velcade; Drug: Thalidomide; Drug: Dexamethasone; Drug: Panobinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLTs)
The number of participants experiencing DLTs within the first cycle of VTD-pano will be presented, with descriptive summaries of the specific DLTs observed. Summaries will be presented for each dose level.
Measured: From cycle 1 day 1 up to the administration of cycle 2 day 1 (up to 22 days)
Proportion o f participants achieving at least partial response
The proportion of participants achieving at least a partial response within 16 cycles of VTD-pano will be presented, with corresponding 80% and 95% confidence intervals
Measured: within 16 cycles of therapy (an expected average of 48 weeks)
Secondary outcomes (8)
Safety and toxicity
The proportion of participants experiencing DLTs and other toxicities, overall and by cycle as graded by CTCAE V4.0.
Measured: Throughout the trial, expected to be 3 years
Proportion of patients with each maximum response category
The number and proportion of participants in each response category within 16 cycles of VTD-pano will be presented with corresponding 95% confidence intervals.
Measured: within 16 cycles of therapy (an expected average of 48 weeks)
Time to maximum response to therapy
Time to maximum response is defined as the time from registration until the patient achieves any of the categories CR, VGPR, PR, MR or SD as their maximum response. Median time to maximum response will be presented.
Measured: from registration until the participant achieves any of the categories CR, VGPR, PR, MR or SD as their maximum response (up to 100 weeks - 48 weeks of treatment plus 52 weeks maintenance)
Progression free survival
A progression-free survival curve will be calculated using the Kaplan Meier method and median PFS estimates will be presented.
Measured: from registration to first documented evidence of disease progression or death (up to 100 weeks)
Compliance to therapy
Compliance to therapy will be summarised descriptively, including number of doses missed and number of dose reductions throughout the treatment period.
Measured: from initial treatment received as per protocol until treatment withdrawal (up to 100 weeks)
Feasibility of panobinostat maintenance
The duration of maintenance and reasons for stopping will be summarised
Measured: up to 12 months
Overall survival
Overall survival (OS) curves will be calculated using the Kaplan Meier method. Median OS, and OS estimates at 12 months, will be presented, if appropriate.
Measured: from registration to date of death
The proportion of participants mobilising sufficient stem cells for transplant(out of those undergoing mobilisation)
To be determined by the satisfactory collection of sufficient numbers of stem cells to support high-dose chemotherapy.
Measured: up to 16 cycles of therapy (an expected average of 48 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2014 (estimated)
- Study startJan 2013
- Primary completionJul 2015 (estimated)
- Study completionJan 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof Jamie Cavenagh
- Sponsor type
- University, hospital or other
- Collaborators
- Myeloma UK, Novartis
- Responsible party
- Sponsor-investigator, Prof Jamie Cavenagh, University of Leeds
- Investigators
- Jamie Cavenagh, MRCPath, Principal investigator, St. Bartholomew's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02145715
- Sponsor's protocol ID
- HM12/10174
- Acronym
- MUKsix
- Status last verified
- Jun 2015
- First submitted
- 1 Mar 2013
- Last updated
- 26 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Popat R, Brown SR, Flanagan L, Hall A, Gregory W, Kishore B, Streetly M, Oakervee H, Yong K, Cook G, Low E, Cavenagh J; Myeloma UK Early Phase Clinical Trial Network. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2016 Dec;3(12):e572-e580. doi: 10.1016/S2352-3026(16)30165-X. Epub 2016 Nov 12.
PubMed 27843120
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Trial of VTD-panobinostat Treatment and Panobinostat Maintenance in Relapsed and Relapsed/Refractory Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT02145715
- Acronym / sponsor ID
- MUKsix / HM12/10174
- Conditions
- Multiple Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Prof Jamie CavenaghUniversity, hospital or other
- Collaborators
- Myeloma UK, Novartis
- Study start
- Jan 2013
- Primary completion
- Jul 2015 (estimated)
- Study completion
- Jan 2016 (estimated)
- First posted
- 23 May 2014 (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.
Velcade (bortezomib), thalidomide and dexamethasone (VTD) has been demonstrated to be a highly effective combination in both patients with previously untreated and those with relapsed multiple myeloma. In previously untreated patients VTD demonstrated clear superiority to TD as induction therapy prior to planned tandem autologous stem cell transplant.
The rationale of this trial is to combine a 'gold standard' antiMM combination with the HDAC inhibitor Panobinostat. There is emerging data to support the concept of clinical synergy between BTZ and HDACi's.
The purpose of this study is to determine the maximum tolerated dose (MTD) and estimated response rates of panobinostat, administered in combination with VTD, in subjects with relapsed and relapsed/refractory multiple myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Velcade, Thalidomide, Dexamethasone (VTD) + Panobinostat | Experimental | Drug: Velcade, Drug: Thalidomide, Drug: Dexamethasone, Drug: PanobinostatUp to 16 cycles of VTD+Panobinostat followed by panobinostat maintenance for 1 year or until disease progression. * Induction - Cycles 1-16 (21-day cycle) * Velcade: 1.3mg/m2 (subcutaneous) on days 1 and 8 * Thalidomide: 100mg (PO)on days 1 -21 * Dexamethasone: 20 mg (PO) on days 1, 2, 8 and 9 * Panobinostat: 10mg, 15mg or 20mg days 1, 3, 5, 8, 10 and 12 Dose depends on cohort entry at registration during the dose escalation phase. The recommended dose will be used during the expansion phase. * Panobinostat monotherapy maintenance for 1 year. Panobinostat will be given at the same dose as the recommended dose during expansion phase |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients with a previous diagnosis of multiple myeloma based on IMWG 2003 definitions:
- Relapsed and relapsed-and-refractory myeloma who have received 1-4 prior lines and now require further treatment
- Able to give informed consent and willing to follow study protocol
- Aged 18 years or over
- ECOG Performance Status ≤2
Key exclusion criteria (10 listed)
- Pregnant (positive pregnancy test) or breastfeeding women.
- Non-secretory Multiple Myeloma 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 160 mg 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.
- 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.
- 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
- 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 clinically significant QTc abnormalities)
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 |
|---|---|---|
| VelcadeAlso: Bortezomib | Drug | Velcade, Thalidomide, Dexamethasone (VTD) + Panobinostat |
| Thalidomide | Drug | Velcade, Thalidomide, Dexamethasone (VTD) + Panobinostat |
| Dexamethasone | Drug | Velcade, Thalidomide, Dexamethasone (VTD) + Panobinostat |
| Panobinostat | Drug | Velcade, Thalidomide, Dexamethasone (VTD) + Panobinostat |
Primary outcome
Dose limiting toxicities (DLTs)
Time frame: From cycle 1 day 1 up to the administration of cycle 2 day 1 (up to 22 days)
The number of participants experiencing DLTs within the first cycle of VTD-pano will be presented, with descriptive summaries of the specific DLTs observed. Summaries will be presented for each dose level.
Proportion o f participants achieving at least partial response
Time frame: within 16 cycles of therapy (an expected average of 48 weeks)
The proportion of participants achieving at least a partial response within 16 cycles of VTD-pano will be presented, with corresponding 80% and 95% confidence intervals
8 secondary outcomes
Safety and toxicity
Time frame: Throughout the trial, expected to be 3 years
Proportion of patients with each maximum response category
Time frame: within 16 cycles of therapy (an expected average of 48 weeks)
Time to maximum response to therapy
Time frame: from registration until the participant achieves any of the categories CR, VGPR, PR, MR or SD as their maximum response (up to 100 weeks - 48 weeks of treatment plus 52 weeks maintenance)
Progression free survival
Time frame: from registration to first documented evidence of disease progression or death (up to 100 weeks)
Compliance to therapy
Time frame: from initial treatment received as per protocol until treatment withdrawal (up to 100 weeks)
Feasibility of panobinostat maintenance
Time frame: up to 12 months
Overall survival
Time frame: from registration to date of death
The proportion of participants mobilising sufficient stem cells for transplant(out of those undergoing mobilisation)
Time frame: up to 16 cycles of therapy (an expected average of 48 weeks)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2015.
- Derived from this study: PubMed 27843120Popat R, Brown SR, Flanagan L, Hall A, Gregory W, Kishore B, Streetly M, Oakervee H, Yong K, Cook G, Low E, Cavenagh J; Myeloma UK Early Phase Clinical Trial Network. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2016 Dec;3(12):e572-e580. doi: 10.1016/S2352-3026(16)30165-X. Epub 2016 Nov 12.
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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.
Jamie Cavenagh, MRCPath principal investigator
St. Bartholomew's Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Velcade, Thalidomide and Dexamethasone in people with Multiple Myeloma, run by Prof Jamie Cavenagh at 5 sites 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 22 inclusion and 10 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 26 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Dose limiting toxicities (DLTs) (time frame: From cycle 1 day 1 up to the administration of cycle 2 day 1 (up to 22 days)). 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 NCT02145715, which also lists 1 linked publication.
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 26 Jun 2015.