- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01720875
Vorinostat, Bortezomib and Dexamethasone in Multiple Myeloma (MUKFour) (MUKfour)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Southampton, United Kingdom, SO16 6YD
- University Hospital Southampton
-
-
Nottinghamshire
-
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
- Nottingham University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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
- 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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Vorinostat Velcade Dexamethasone (VVD)
Up to 8 cycles of VVD followed by vorinostat maintenance until disease progression. Cycles 1-8 (21-day cycle)
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
up to 24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of dose reductions during treatment with vorinostat, bortezomib and dexamethasone.
Time Frame: up to 24 weeks
|
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.
|
up to 24 weeks
|
Overall numbers and rates of adverse events
Time Frame: Up to 18 months
|
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.
|
Up to 18 months
|
Progression free survival
Time Frame: Up to 18 months
|
A progression-free survival curve will be calculated using the Kaplan Meier method and median PFS estimates will be presented
|
Up to 18 months
|
Maximum response to treatment
Time Frame: Up to 24 weeks
|
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
|
Up to 24 weeks
|
Time to maximum response
Time Frame: Up to 18 months
|
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.
|
Up to 18 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Matched pairs analysis
Time Frame: Up to 24 months
|
A matched pairs analysis will be carried out looking at overall response, PFS, dose reductions and toxicity in participants treated with vorinostat in combination with bortezomib and dexamethasone (VVD) in this current study compared to participants randomised to the bortezomib/vorinostat (VV) arm in the pivotal MSD phase III study.
|
Up to 24 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Matthew Jenner, University Hospital of Southampton
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Histone Deacetylase Inhibitors
- Dexamethasone
- Bortezomib
- Vorinostat
Other Study ID Numbers
- HM11/10041
- ISRCTN08577602 (Registry Identifier: ISRCTN)
- 2011-005361-20 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on Vorinostat Velcade Dexamethasone
-
University of VirginiaCompletedNon Small Cell Lung CancerUnited States
-
The Methodist Hospital Research InstituteWithdrawnNon-Hodgkin Lymphoma
-
University of Wisconsin, MadisonMerck Sharp & Dohme LLC; Millennium Pharmaceuticals, Inc.CompletedCarcinoma, Non Small Cell Lung
-
Masonic Cancer Center, University of MinnesotaMerck Sharp & Dohme LLC; Millennium Pharmaceuticals, Inc.TerminatedLeukemia | Myelodysplastic SyndromeUnited States
-
National Cancer Institute (NCI)CompletedSarcoma | Lymphoma | Neuroblastoma | WilmsTumorUnited States
-
Merck Sharp & Dohme LLCCompleted
-
National Cancer Institute (NCI)CompletedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Merck Sharp & Dohme LLCCompleted
-
National Cancer Institute (NCI)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)CompletedAdult Giant Cell Glioblastoma | Adult Glioblastoma | Adult Gliosarcoma | Recurrent Adult Brain TumorUnited States