A Pilot Study of Oral Vorinostat Plus Oral Eltrombopag Support in Patients With Lymphoma (VEIL)
- 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
- 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
- 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
- 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.