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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01500538




Registration number
NCT01500538
Ethics application status
Date submitted
22/12/2011
Date registered
28/12/2011
Date last updated
15/02/2016

Titles & IDs
Public title
A Pilot Study of Oral Vorinostat Plus Oral Eltrombopag Support in Patients With Lymphoma (VEIL)
Scientific title
A Pilot Study of Oral Vorinostat Plus Oral Eltrombopag Support in Patients With Lymphoma (VEIL)
Secondary ID [1] 0 0
11/111
Universal Trial Number (UTN)
Trial acronym
VEIL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma 0 0
Marginal Zone Lymphoma 0 0
Mantle Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eltrombopag and Vorinostat

Experimental: Eltrombopag and vorinostat combination therapy - Daily oral intake of 400mg vorinostat if necessary with combination therapy eltrombopag commencing at 50mg per day increasing to a maximum of 200mg per day


Treatment: Drugs: Eltrombopag and Vorinostat
4 week mono-therapy eltrombopag, commencing at 50mg/day, increasing to 200mg. Daily intake of 400mg vorinostat for minimum of 6 cycles, each cycle of 4 weeks, possibly in combination with daily intake eltrombopag commencing at 50mg/day at a maximum dose of 200md/day (150mg/day for subjects of East-Asian ancestry)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The occurrence of all grade III/IV adverse events (haematological and non haematological) during vorinostat and eltrombopag combination therapy - The period of observation for the primary endpoint is defined as the observation for 6 cycles of eligible patients who have commencement eltrombopag following commencement of vorinostat.
Timepoint [1] 0 0
One year from trial entry
Secondary outcome [1] 0 0
Occurrence of thrombocytopenia (TCP) with vorinostat therapy and response to eltrombopag: platelet, transfusion and bleeding endpoints - Occurrence & severity of thrombocytopenia (TCP), all grades at baseline & during first 6 vorinostat cycles.
Occurrence & severity of worsening grade of TCP (relative to day 1 cycle 1 of vorinostat therapy) after cycle 1 day 8.
Occurrence & severity of TCP following withdrawal of eltrombopag in patients who had protocol-specified withdrawal of eltrombopag.
Occurrence of platelet response, defined as a cycle nadir platelet count showing a 50% improvement in platelet nadir compared to previous cycle & at least an absolute increase of 20x109/L.
Occurrence of grade III/IV TCP during vorinostat treatment cycle among patients who experience a platelet nadir =25 x109/L, receive eltrombopag & who then achieve a platelet response.
Percentage drop in platelet count from day 1 of cycle to nadir & percentage drop in neutrophil count from day 1 of cycle to nadir, for each cycle.
Occurrence & severity of clinically significant bleeding events defined as per the WHO bleeding scale.
Timepoint [1] 0 0
One year from trial entry

Eligibility
Key inclusion criteria
- Age 18years or older

- T-cell lymphoma involving the skin or patients with relapsed/refractory follicular
lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL). Disease
must have been confirmed by previous histology and must be measurable

- For patients with cutaneous T-cell lymphoma: At least 2 prior systemic therapies
(including 1 month of therapy with systemic steroids >25mg alternating days of
prednisolone or equivalent, or total skin electron-beam radiotherapy). For patients
with B cell lymphoma, prior exposure to a chemotherapy regimen is required, unless the
patient is deemed to be unfit for conventional chemo-therapeutic regimens.

- Adequate haematological function: ANC = 1.0x109/L

- Adequate renal function (serum creatinine clearance calculated as CrCl =30mL/min
(perform 24hr urine creatinine clearance if serum creatinine is >1.5xULN);electrolyte
levels = LLN (i.e.: potassium, total calcium [corrected for serum albumin], magnesium
and phosphorus) or correctable with supplements)

- Adequate hepatic function:AST and ALT = 2.5 x ULN (or = 5.0 x ULN if liver
infiltration;Serum bilirubin = 1.5 x ULN

- Life expectancy = 12 weeks

- Written informed consent obtained prior to any study specific screening procedures

- ECOG performance status grade 0-2

- Ability to comply with adequate contraception in patients of childbearing potential.

- Females of childbearing potential must have had a negative urine pregnancy test at
screening and agree to use a medically reliable method of preventing conception
throughout the study and for 30 days following the date of last dose.

- Males with a female partner of childbearing potential must agree to use a medically
reliable method of preventing conception throughout the study and for 30 days
following the date of last dose.

- Mentally competent and is able to understand the information given and provide
informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known uncontrolled medical conditions which may compromise participation in this study
including but not limited to:Poorly controlled congestive heart failure: ejection
fraction <30% measured in past 6 months) or NYHA class IV;Unstable angina or an
ischaemic cardiac event requiring hospital admission in the previous 12 months.

- Concomitant use of another HDAC inhibitor, including sodium valproate.

- GI disease that may significantly alter the absorption of eltrombopag

- Subjects known to be seropositive for HIV, Hepatitis B or Hepatitis C.

- Current participation in other trials or studies of medical therapeutic interventions.

- Known pro-thrombotic condition as defined by a history =1 unprovoked deep venous
thrombosis or pulmonary embolism, or any DVT/PE with a procoagulant condition screen
suggesting the presence of a procoagulant condition (prothrombin gene mutation
homozygosity, factor V Leiden homozygosity, antithrombin deficiency, lupus
anticoagulant syndrome).

- History of ischaemic neurological event (TIA or stroke) within the preceding 2 years.

- Active or uncontrolled infection, other than cutaneous infection.

- Prior diagnosis of cancer that was:more than 5 years prior to current diagnosis with
subsequent evidence of disease recurrence or estimated clinical expectation of
recurrence is greater than 10% within next 2 years;within 5 years of current diagnosis
with the exception of successfully treated basal cell or squamous cell skin carcinoma,
carcinoma in situ of the cervix or localised cancer treated curatively with local
therapy only

- Use of another anti-cancer treatment within 21 days of starting vorinostat, with the
exception of steroids, interferon or oral methotrexate which have been at a stable
dose for at least 4 weeks prior to day 1.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Merck Sharp & Dohme Corp.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Vorinostat is a drug (Histone Deacetylase Inhibitor [HDACi]) administered orally that has
been approved in United States for the patients with cutaneous Tcell lymphoma (CTCL) who have
progressive, persistent or recurrent disease on or following two systemic therapies.

In the early period of treatment with vorinostat, some patients may experience low platelet
counts. Therefore this study will be examining the combination of these two medications
(Vorinostat and eltrombopag) to assess if eltrombopag can overcome the low platelets during
treatment with vorinostat.

Eltrombopag is a drug administered orally designed to mimic the protein thrombopoietin, which
causes the body to make more platelets. Eltrombopag has been registered in Australia and
approved overseas to treat patients with chronic ITP (Immune Thrombocytopenia Purpura) a
disease where patients destroy their own platelets very rapidly and thus develop low platelet
count) but it is not registered and it is not yet known whether eltrombopag can increase
platelet counts in patients treated with the HDACi.

The aim of this project is to test whether Vorinostat and eltrombopag can be safely combined,
and to test whether they are effective in participants with T-cell lymphoma involving the
skin or patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma
(MZL), or mantle cell lymphoma (MCL)

A total of 25 people with Cutaneous T cell lymphoma/ CTCL, marginal zone lymphoma, follicular
lymphoma or mantle cell lymphoma will be recruited in this study.
Trial website
https://clinicaltrials.gov/show/NCT01500538
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Dickinson, MBBS (Hons), FRCPA
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01500538