Vorinostat, Bortezomib and Dexamethasone in Multiple Myeloma (MUKFour)

Multiple Myeloma Clinical Trial

— MUKfour  

Official title:

A Phase II Trial of Combination Treatment With Vorinostat, Bortezomib and Dexamethasone in Patients With Relapsed and Relapsed Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01720875
• Other study ID #: HM11/10041
• Secondary ID: ISRCTN0857760220
• Status: Completed
• Phase: Phase 2
• Start date: August 9, 2013
• Est. completion date: August 29, 2018

Study information

• Verified date: August 2021
• Source: University of Leeds
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 29, 2018
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Vorinostat Velcade Dexamethasone

Locations

Country	Name	City	State
United Kingdom	Nottingham University Hospital	Nottingham	Nottinghamshire
United Kingdom	University Hospital Southampton	Southampton

Sponsors (3)

Lead Sponsor	Collaborator
University of Leeds	Merck Sharp & Dohme Corp., Myeloma UK

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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: Result — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Matched pairs analysis	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
Primary	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.	up to 24 weeks
Secondary	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.	up to 24 weeks
Secondary	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.	Up to 18 months
Secondary	Progression free survival	A progression-free survival curve will be calculated using the Kaplan Meier method and median PFS estimates will be presented	Up to 18 months
Secondary	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	Up to 24 weeks
Secondary	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.	Up to 18 months