Vorinostat, Bortezomib and Dexamethasone in Multiple Myeloma (MUKFour)

NCT ID: NCT01720875

Last Updated: 2021-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-09
• Study Completion Date: 2018-08-29

Brief 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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vorinostat Velcade Dexamethasone (VVD)

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

Group Type: EXPERIMENTAL

Vorinostat Velcade Dexamethasone

Intervention Type: DRUG

Interventions

Vorinostat Velcade Dexamethasone

Intervention Type: DRUG

Other Intervention Names

Bortezomib (velcade)

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Myeloma UK

OTHER

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Leeds

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Jenner

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Southampton

Locations

Nottingham University Hospital

Nottingham, Nottinghamshire, United Kingdom

University Hospital Southampton

Southampton, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 33478922 (View on PubMed)

Other Identifiers

ISRCTN08577602

Identifier Type: REGISTRY

Identifier Source: secondary_id

2011-005361-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HM11/10041

Identifier Type: -

Identifier Source: org_study_id