Vorinostat in combination with bortezomib and dexamethasone in patients with relapsed and relapsed refractory multiple myeloma
| ISRCTN | ISRCTN08577602 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN08577602 |
| EudraCT/CTIS number | 2011-005361-20 |
| ClinicalTrials.gov number | NCT01720875 |
| Secondary identifying numbers | HM11/10041 |
- Submission date
- 31/10/2011
- Registration date
- 01/03/2012
- Last edited
- 30/05/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Dr Faith Davies
Scientific
Scientific
Haemato-Oncology Unit
Royal Marsden NHS Foundation Trust
Downs Road
Sutton
SM2 5PT
United Kingdom
Study information
| Study design | Open-label multi-centre single-arm Phase II trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format please use the contact details to request a patient information sheet |
| Scientific title | A Phase II trial of vorinostat in combination with bortezomib and dexamethasone in patients with relapsed and relapsed refractory multiple myeloma |
| Study objectives | Aim: To assess the overall response rate of patients with relapsed or refractory and refractory multiple myeloma after induction treatment with vorinostat in combination with bortezomib and dexamethasone. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Relapsed or relapsed and refractory multiple myeloma |
| Intervention | All trial participants will receive the same treatment regimen as follows: Cycles 1- 8 (21-day cycle): 1. Bortezomib: 1.3 mg/m2 IV on days 1,4, 8 and 11 2. Dexamethasone: 20 mg PO on days 1, 2, 4, 5, 8, 9, 11 and 12 3. Vorinostat: 400 mg PO on days 1-14 Maintenance (28-day cycle): Vorinostat: 400 mg PO on 1-7 and 15-21 Maintenance will continue until disease progression or intolerance |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Vorinostat, bortezomib, dexamethasone |
| Primary outcome measure | Proportion of patients achieving at least a partial response (PR) within 8 cycles of protocol treatment, as defined by modified International Working Group (IWG) criteria |
| Secondary outcome measures | 1. Safety, toxicity and tolerability 2. Progression-free survival 3. Proportion of patients achieving at least a very good partial response (VGPR) within 8 cycles of treatment 4. Maximum response of patients to treatment overall and after 8 treatment cycles 5. Time to maximum response 6. Quality of life |
| Overall study start date | 01/03/2012 |
| Completion date | 01/03/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 68 |
| Total final enrolment | 16 |
| Key inclusion criteria | 1. Able to give informed consent and willing to follow study protocol and quality of life assessments 2. Aged 18 years or over 3. Subjects with multiple myeloma diagnosed according to standard criteria, who require further treatment due to relapse or non-response after at least one but not more than three prior lines of treatment 4. Patients with measurable extramedullary plasmacytomas are allowed if they fulfil the above inclusion criteria 5. No prior Histone deacetylases (HDAC) inhibitor treatment. Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumour therapy must not be enrolled in this study. (Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enrol after a 30-day washout period.) 6. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2 7. Required laboratory values within 21 days of registration 7.1. Absolute neutrophil count ≥1.0 x 10e9/L 7.2. Platelet count ≥75 x 10e9/L 7.3. Haemoglobin >9 g/dL 7.4. Bilirubin ≤1.5 x upper limit of normal 7.5. ALT and/or AST ≤2.5 x upper limit of normal 7.6. Serum creatinine ≤2.0 x upper limit of normal 7.7. Corrected calcium ≤2.8 mmol/L 8. Life expectancy of at least 3 months 9. Female subjects of childbearing 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 10. Patient is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis |
| Key exclusion criteria | 1. Pregnant or breastfeeding females 2. 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. 3. 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. Patients with histories (≥12 months) of other tumours may be entered 4. Patients considered to be refractory to prior bortezomib treatment (defined below) or unable to tolerate treatment with bortezomib. 4.1. Relapse on or within 60 days after the last dose of a bortezomib-containing regimen 4.2. No clinical response (≤SD/NC) on a bortezomib-containing regimen 4.3. Peripheral neuropathy of ≥ grade 2 severity 4.4. Patient has plasma cell leukaemia defined as the presence of more than 20% plasma cells in the peripheral blood and/or an absolute plasma cell count of ≥2000/μL 4.5. 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. 4.6. Patients with significant cardiovascular disease (e.g. acute diffuse infiltrative pulmonary disease, pericardial disease, a 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 4.7. Active symptomatic fungal, bacterial, and/or viral infection, including known active HIV or known viral (A, B, or C) hepatitis 5. Unable to take corticotherapy at study entry 6. Patient with prior allogeneic bone marrow transplant 7. Patient has known hypersensitivity to any components of bortezomib (such as boron, mannitol) or vorinostat 8. Patient has known central nervous system (CNS) metastases and/or carcinomatous meningitis 9. 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) |
| Date of first enrolment | 01/03/2012 |
| Date of final enrolment | 01/03/2013 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Haemato-Oncology Unit
Sutton
SM2 5PT
United Kingdom
SM2 5PT
United Kingdom
Sponsor information
University of Leeds (UK)
University/education
University/education
Research and Development
34 Hyde Terrace
Leeds
LS2 9LN
England
United Kingdom
| Website | http://www.leeds.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/024mrxd33 |
Funders
Funder type
Charity
Myeloma UK (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 03/12/2015 | Yes | No | |
| Results article | 01/03/2021 | 31/03/2021 | Yes | No | |
| Plain English results | 30/05/2025 | No | Yes |
Editorial Notes
30/05/2025: Cancer Research UK plain English results link added.
31/03/2021: Publication reference added.
23/04/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
30/09/2016: No publications found, verifying study status with principal investigator
