Vorinostat, Bortezomib and Dexamethasone in Multiple Myeloma (MUKFour) (MUKfour)

This is an interventional treatment trial for Multiple Myeloma Read More

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)