Multiple MyelomaPhase 2MUKfourNCT01720875
Vorinostat, Bortezomib and Dexamethasone in Multiple Myeloma (MUKFour)
A Phase 2 study testing Vorinostat Velcade Dexamethasone in people with Multiple Myeloma, run by University of Leeds at 2 sites in United Kingdom.
Trial summary
Bortezomib is an established treatment in multiple myeloma; it is common practice in the UK to administer bortezomib with dexamethasone. This practice is based on data that supports improved response rates with this combination. 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?
- Vorinostat Velcade Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 9 Aug 2013to 29 Aug 2018
- Phase
- Phase 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
- Able to give informed consent - Aged 18 years or over
- Participants with relapsed myeloma who have received 1-3 prior lines of treatment and now require further treatment
- ECOG Performance Status ≤ 2
- Required laboratory values within 14 days of registration:
- Absolute neutrophil count ≥1.0 x 10^9/L.
- Platelet count ≥75x10^9/L.
Show all 14Show fewer
- Haemoglobin > 9 g/dL.
- Bilirubin ≤1.5 x upper limit of normal
- ALT and / or AST ≤2.5 x upper limit of normal
- Serum creatinine ≤ 2.0 x upper limit of normal
- Corrected calcium ≤ 2.8 mmol/L
- Life expectancy of at least 3 months
- Female participants 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 participants 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
- Participant is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis.
Who cannot join
- 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 to stop rapid relapse during this period is permitted, but must be stopped 7 days prior to study drug administration.
- Prior HDAC inhibitor treatment.
- Previous or concurrent active malignancies (<12 months post end of treatment) at other sites with the exception of appropriately treated localised epithelial skin or cervical cancer.
- Participants considered to be refractory to prior bortezomib treatment or unable to tolerate treatment with bortezomib.
- Peripheral neuropathy of ≥ grade 2 severity
- Participants who have received growth factor support or platelet support within 14 days prior to registration
Show all 14Show fewer
- Participants with uncontrolled concurrent illness or circumstances that could limit compliance with the study.
- Patients with significant cardiovascular or pulmonary disease
- Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis.
- Pregnant or breast feeding females
- Unable to take corticosteroid therapy at study entry
- Participants with known hypersensitivity to any components of bortezomib, (such as boron, mannitol), vorinostat or dexamethasone.
- Participant has known CNS metastases and/or carcinomatous meningitis.
- Participants with a history of a gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s)
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Nottingham University Hospital
Nottingham, Nottinghamshire, NG5 1PB
University Hospital Southampton
Southampton, SO16 6YD
About this study
Official title: A Phase II Trial of Combination Treatment With Vorinostat, Bortezomib and Dexamethasone in Patients With Relapsed and Relapsed Refractory Multiple Myeloma
Bortezomib is an established treatment in multiple myeloma; it is common practice in the UK to administer bortezomib with dexamethasone. This practice is based on data that supports improved response rates with this combination.
Recent trial data indicates that the addition of vorinostat to bortezomib treatment overcomes treatment resistance to bortezomib. As such this current trial is designed to investigate the efficacy, safety and tolerability of combination treatment with vorinostat, bortezomib and dexamethasone in patients with relapsed and relapsed refractory myeloma.
A comparison of this Phase II trial with the pivotal Phase III trial conducted by MSD (using the labelled bortezomib indication without dexamethasone) will address the impact of dexamethasone in regards to tolerability and additional efficacy in myeloma patients.
- Conditions
- Multiple Myeloma
- Being tested
- Vorinostat Velcade Dexamethasone
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vorinostat Velcade DexamethasoneDrug
Also called Bortezomib (velcade)
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat Velcade Dexamethasone (VVD) | Experimental | Up to 8 cycles of VVD followed by vorinostat maintenance until disease progression.
Cycles 1-8 (21-day cycle)
* Velcade: 1.3mg/m2 (subcutaneous) on days 1, 4, 8 and 11
* Dexamethasone: 20 mg (PO) on days 1, 2, 4, 5, 8, 9, 11 and 12
* Vorinostat: 400mg (PO) on days 1-4, 8-11, 15-18 Maintenance (28-day cycle)
* Vorinostat: 400mg PO on 1-4 and 15-18 Receives: Drug: Vorinostat Velcade Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate to vorinostat, bortezomib and dexamethasone.
To assess the number and proportion of participants with at least a partial response (PR) or better within 8 cycles of protocol treatment with vorinostat, bortezomib and dexamethasone.
Measured: up to 24 weeks
Secondary outcomes (5)
Number of dose reductions during treatment with vorinostat, bortezomib and dexamethasone.
To assess the dose reduction profile of combination treatment with vorinostat, bortezomib and dexamethasone. The proportion of participants experiencing a dose reduction or terminating treatment early due to toxicity will be assessed.
Measured: up to 24 weeks
Overall numbers and rates of adverse events
Safety and toxicity analyses will summarise the overall serious adverse event and adverse events rates including the number and proportion of participants with at least one safety event. SAEs will be additionally presented by the relationship to study treatment, seriousness criteria, event outcome, duration and by MedDRA body system coding.
Measured: Up to 18 months
Progression free survival
A progression-free survival curve will be calculated using the Kaplan Meier method and median PFS estimates will be presented
Measured: Up to 18 months
Maximum response to treatment
The overall number and proportion of participants in each response category within 8 cycles of treatment and overall across all treatment including the maintenance phase
Measured: Up to 24 weeks
Time to maximum response
The time to maximum response will be calculated from the date of registration to the date of maximum response. Participant's who progress and do not achieve a maximum response will be censored at the time of progression. Median time to maximum response will be presented.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2012 (estimated)
- Study start9 Aug 2013
- Primary completionAug 2015
- Study completion29 Aug 2018
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- Myeloma UK, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Matthew Jenner, Principal investigator, University Hospital of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01720875
- Sponsor's protocol ID
- HM11/10041
- Other IDs
- ISRCTN08577602, 2011-005361-20
- Acronym
- MUKfour
- Status last verified
- Aug 2021
- First submitted
- 31 Oct 2012
- Last updated
- 16 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Brown S, Pawlyn C, Tillotson AL, Sherratt D, Flanagan L, Low E, Morgan GJ, Williams C, Kaiser M, Davies FE, Jenner MW; Myeloma UK Early Phase Clinical Trial Network. Bortezomib, Vorinostat, and Dexamethasone Combination Therapy in Relapsed Myeloma: Results of the Phase 2 MUK four Trial. Clin Lymphoma Myeloma Leuk. 2021 Mar;21(3):154-161.e3. doi: 10.1016/j.clml.2020.11.019. Epub 2020 Dec 3.
PubMed 33478922
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Combination Treatment With Vorinostat, Bortezomib and Dexamethasone in Patients With Relapsed and Relapsed Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01720875
- Acronym / sponsor ID
- MUKfour / HM11/10041
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- Myeloma UK, Merck Sharp & Dohme LLC
- Study start
- 9 Aug 2013 (actual)
- Primary completion
- Aug 2015 (actual)
- Study completion
- 29 Aug 2018 (actual)
- First posted
- 2 Nov 2012 (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.
Bortezomib is an established treatment in multiple myeloma; it is common practice in the UK to administer bortezomib with dexamethasone. This practice is based on data that supports improved response rates with this combination.
Recent trial data indicates that the addition of vorinostat to bortezomib treatment overcomes treatment resistance to bortezomib. As such this current trial is designed to investigate the efficacy, safety and tolerability of combination treatment with vorinostat, bortezomib and dexamethasone in patients with relapsed and relapsed refractory myeloma.
A comparison of this Phase II trial with the pivotal Phase III trial conducted by MSD (using the labelled bortezomib indication without dexamethasone) will address the impact of dexamethasone in regards to tolerability and additional efficacy in myeloma patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat Velcade Dexamethasone (VVD) | Experimental | Drug: Vorinostat Velcade DexamethasoneUp to 8 cycles of VVD followed by vorinostat maintenance until disease progression. Cycles 1-8 (21-day cycle) * Velcade: 1.3mg/m2 (subcutaneous) on days 1, 4, 8 and 11 * Dexamethasone: 20 mg (PO) on days 1, 2, 4, 5, 8, 9, 11 and 12 * Vorinostat: 400mg (PO) on days 1-4, 8-11, 15-18 Maintenance (28-day cycle) * Vorinostat: 400mg PO on 1-4 and 15-18 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Able to give informed consent - Aged 18 years or over
- Participants with relapsed myeloma who have received 1-3 prior lines of treatment and now require further treatment
- ECOG Performance Status ≤ 2
- Required laboratory values within 14 days of registration:
- Life expectancy of at least 3 months
Key exclusion criteria (14 listed)
- 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 to stop rapid relapse during this period is permitted, but must be stopped 7 days prior to study drug administration.
- Prior HDAC inhibitor treatment.
- Previous or concurrent active malignancies (<12 months post end of treatment) at other sites with the exception of appropriately treated localised epithelial skin or cervical cancer.
- Participants considered to be refractory to prior bortezomib treatment or unable to tolerate treatment with bortezomib.
- Peripheral neuropathy of ≥ grade 2 severity
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 |
|---|---|---|
| Vorinostat Velcade DexamethasoneAlso: Bortezomib (velcade) | Drug | Vorinostat Velcade Dexamethasone (VVD) |
Primary outcome
Overall response rate to vorinostat, bortezomib and dexamethasone.
Time frame: up to 24 weeks
To assess the number and proportion of participants with at least a partial response (PR) or better within 8 cycles of protocol treatment with vorinostat, bortezomib and dexamethasone.
5 secondary outcomes
Number of dose reductions during treatment with vorinostat, bortezomib and dexamethasone.
Time frame: up to 24 weeks
Overall numbers and rates of adverse events
Time frame: Up to 18 months
Progression free survival
Time frame: Up to 18 months
Maximum response to treatment
Time frame: Up to 24 weeks
Time to maximum response
Time frame: Up to 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
- Results publication: PubMed 33478922Brown S, Pawlyn C, Tillotson AL, Sherratt D, Flanagan L, Low E, Morgan GJ, Williams C, Kaiser M, Davies FE, Jenner MW; Myeloma UK Early Phase Clinical Trial Network. Bortezomib, Vorinostat, and Dexamethasone Combination Therapy in Relapsed Myeloma: Results of the Phase 2 MUK four Trial. Clin Lymphoma Myeloma Leuk. 2021 Mar;21(3):154-161.e3. doi: 10.1016/j.clml.2020.11.019. Epub 2020 Dec 3.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Matthew Jenner principal investigator
University Hospital of Southampton
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vorinostat Velcade Dexamethasone in people with Multiple Myeloma, run by University of Leeds at 2 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 14 inclusion and 14 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: finished, as of the sponsor's last update on 16 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall response rate to vorinostat, bortezomib and dexamethasone. (time frame: up to 24 weeks). 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 NCT01720875, 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 16 Aug 2021.