NCT01500538

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 Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Oct 2012

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 22, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 28, 2011

Completed
9 months until next milestone

Study Start

First participant enrolled

October 1, 2012

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2013

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

February 15, 2016

Status Verified

October 1, 2012

Enrollment Period

7 months

First QC Date

December 22, 2011

Last Update Submit

February 12, 2016

Conditions

Follicular LymphomaMarginal Zone LymphomaMantle Cell Lymphoma

Keywords

Follicular lymphomaMarginal zone lymphomaMantle cell lymphomathrombocytopeniaeltrombopagvorinostatlymphoma

Outcome Measures

Primary Outcomes (1)

  • 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.

    One year from trial entry

Secondary Outcomes (1)

  • Occurrence of thrombocytopenia (TCP) with vorinostat therapy and response to eltrombopag: platelet, transfusion and bleeding endpoints

    One year from trial entry

Study Arms (1)

Eltrombopag and vorinostat combination therapy

EXPERIMENTAL

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

Drug: Eltrombopag and Vorinostat

Interventions

Eltrombopag and VorinostatDRUG

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)

Also known as: Revolade (eltrombopag), Zolinza (vorinostat)
Eltrombopag and vorinostat combination therapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

MeSH Terms

Conditions

Lymphoma, FollicularLymphoma, B-Cell, Marginal ZoneLymphoma, Mantle-CellThrombocytopeniaLymphoma

Interventions

eltrombopagVorinostat

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-CellBlood Platelet DisordersHematologic DiseasesCytopenia

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic Acids

Study Officials

  • Michael Dickinson, MBBS (Hons), FRCPA

    Peter MacCallum Cancer Centre, Australia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 22, 2011

First Posted

December 28, 2011

Study Start

October 1, 2012

Primary Completion

May 1, 2013

Study Completion

May 1, 2014

Last Updated

February 15, 2016

Record last verified: 2012-10

Locations

AU(1)