Condition category
Cancer
Date applied
31/10/2011
Date assigned
01/03/2012
Last edited
30/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Faith Davies

ORCID ID

Contact details

Haemato-Oncology Unit
Royal Marsden NHS Foundation Trust
Downs Road
Sutton
SM2 5PT
United Kingdom

Additional identifiers

EudraCT number

2011-005361-20

ClinicalTrials.gov number

NCT01720875

Protocol/serial number

HM11/10041

Study information

Scientific title

A phase II trial of vorinostat in combination with bortezomib and dexamethasone in patients with relapsed and relapsed refractory multiple myeloma

Acronym

Study hypothesis

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

Not provided at time of registration

Study design

Open label multi centre single arm phase II trial

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format please use the contact details below to request a patient information sheet

Condition

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: 1.3mg/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: 400mg PO on days 1-14

Maintenance (28-day cycle):
Vorinostat: 400mg PO on 1-7 and 15-21

Maintenance will continue until disease progression or intolerance

Intervention type

Drug

Phase

Phase II

Drug names

Vorinostat, bortezomib, dexamethasone

Primary outcome measures

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 trial start date

01/03/2012

Overall trial end date

01/03/2013

Reason abandoned

Eligibility

Participant 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 109/L
7.2. Platelet count ≥75x109/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 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
10. Patient is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

68

Participant exclusion criteria

1. Pregnant or breast feeding 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)

Recruitment start date

01/03/2012

Recruitment end date

01/03/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Haemato-Oncology Unit
Sutton
SM2 5PT
United Kingdom

Sponsor information

Organisation

University of Leeds (UK)

Sponsor details

Research and Development
34 Hyde Terrace
Leeds
LS2 9LN
United Kingdom

Sponsor type

University/education

Website

http://www.leeds.ac.uk/

Funders

Funder type

Charity

Funder name

Myeloma UK (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

30/09/2016: No publications found, verifying study status with principal investigator