Vorinostat in Combination with Bortezomib and Dexamethasone in Patients with Relapsed and Relapsed Refractory Multiple Myeloma

Phase 1

• Conditions: Relapsed myeloma.; MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005361-20-GB
• Lead Sponsor: niversity of Leeds

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-12-05
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 68

Inclusion Criteria

• Able to give informed consent and willing to follow study protocol and quality of life assessments
• Aged 18 years or over
• Participants with relapsed multiple myeloma who have received 1-3 prior lines of treatment and now require further treatment
• ECOG Performance Status = 2
• Required laboratory values:
-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 subjects 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 subjects 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
• Patient is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

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. Bisphosphonates for bone disease and radiotherapy for palliative intent are also permitted.
• Prior HDAC inhibitor treatment. Participants who have received compounds with HDAC inhibitor like activity, such as valproic acid, as anti-tumour therapy must not be enrolled in this study. (Participants who have received such compounds for other indications e.g. valproic acid for epilepsy, may enrol after a 30 day washout period)
• Concurrent or previous malignancies (<12 months post end of treatment) at other sites with the exception of appropriately treated localised epithelial skin or cervical cancer. Patients with histories (=12 months) of other tumours may be entered
• Patients considered to be refractory to prior bortezomib treatment, defined as:
-Relapse on OR within 60 days after the last dose of a bortezomib containing regimen
-No clinical response (= SD/NC) on a bortezomib containing regimen.
• Peripheral neuropathy of = grade 2 severity
• Patients who have received growth factor support or platelet support within 14 days prior to registration
• Patient has uncontrolled concurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: acute or chronic graft versus host disease, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within past 6 months, uncontrolled cardiac arrhythmia, renal failure, psychiatric or social conditions that may interfere with patient compliance, or any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient at unacceptable risk for adverse outcome if he/she were to participate in the study.
• Patients with significant cardiovascular disease (e.g. history of congestive heart failure requiring therapy, presence of severe valvular heart disease, presence of an atrial or ventricular arrhythmia requiring treatment, uncontrolled hypertension, a history of QTc abnormalities or with QTC interval > 480 msecs
• 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
• Patient has known hypersensitivity to any components of bortezomib, (such as boron, mannitol), or vorinostat.
• Patient has known CNS metastases and/or carcinomatous meningitis.
• Patient has 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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified