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Peripheral T-cell Lymphoma (Not Otherwise Specified)Phase 2NCT00901147

Study of Bortezomib and Panobinostat in Treating Patients With Relapsed/Refractory Peripheral T-cell Lymphoma or NK/T-cell Lymphoma

A Phase 2 study testing panobinostat and bortezomib in people with Peripheral T-cell Lymphoma (Not Otherwise Specified) and Angioimmunoblastic T-cell Lymphoma, run by Singapore General Hospital at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine whether intravenous Bortezomib combined with oral Panobinostat (LBH589) are effective in treating adult patients with relapsed/refractory peripheral T-cell lymphoma or NK/T-cell lymphoma after the failure of conventional chemotherapy. Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
panobinostat and bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
5 sitesin 3 countries
Study dates
Nov 2009to Jan 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed PTCL NOS, angioimmunoblastic T-cell lymphoma, extranodal NK/T-cell lymphoma nasal type, enteropathy- type T-cell lymphoma, hepatosplenic T-cell lymphoma, ALCL (ALK-1 negative), or patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after ASCT
  • Age ≥21 years
  • Written informed consent
  • Progressive disease following at least one systemic therapy or refractory to at least one prior systemic therapy
  • Measurable disease according to the IWC criteria and/or measurable bone marrow disease by flow cytometry or morphology
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
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  • Absolute neutrophil count of ≥1000 × 10(9)cells/L
  • Serum potassium ≥3.8 mmol/L and magnesium ≥0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria)
  • Negative urine or serum pregnancy test on females of childbearing potential
  • All females of childbearing potential and males must use an effective barrier method of contraception during the treatment period and for at least 1 month thereafter.

Who cannot join

  • Chemotherapy or immunotherapy within 3 weeks of study entry
  • Concomitant use of any other anti-cancer therapy
  • Concomitant use of any other investigational agent
  • Any known cardiac abnormalities such as:
  • Congenital long QT syndrome;
  • QTcF interval >480 milliseconds (msec);
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  • A myocardial infarction within 12 months of study entry;
  • Other significant ECG abnormalities including 2nd atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate < 50 beats/ min).
  • An ECG recorded at screening showing significant ST depression (ST depression of ≥2 mm, measured from isoelectric line to the ST segment at a point 60 msec at the end of the QRS complex). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  • Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction <40% by MUGA scan or <50% by echocardiogram and/or MRI;
  • A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
  • Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above);
  • Any cardiac arrhythmia requiring anti-arrhythmic medication;
  • Serum potassium <3.8 mmol/L or serum magnesium <0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria)
  • Concomitant use of drugs that may cause a prolongation of the QTcF
  • Concomitant use of CYP3A4 inhibitors
  • Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule
  • Concomitant use of warfarin due to a potential drug interaction
  • Clinically significant active infection
  • Known infection with human immunodeficiency virus (HIV)
  • Patient has known clinically active hepatitis B or C
  • Previous extensive radiotherapy involving ≥30% of bone marrow (e.g., whole pelvis, half spine), excluding patients who have had total body irradiation as part of a conditioning regimen for stem cell transplant
  • Major surgery within 2 weeks of study entry
  • Peripheral neuropathy or neuropathic pain of Grade 2 or worse
  • Platelet count <50 × 109 cells/L or platelet count <30 × 109 cells/L if bone marrow disease involvement is documented
  • Serum creatinine >2.0 × ULN
  • Patients who are pregnant or breast-feeding
  • Patient has known hypersensitivity to any components of bortezomib (such as boron, mannitol), or panobinostat

Trial locations and contacts

5 sites in 3 countries.

5 sites in 3 countries

Malaysia2 sites

  • Hospital Universiti Kebangsaan Malaysia ( HUKM )

    Kuala Lumpur, Kuala Lumpur, 56000

  • Subang Jaya Medical Centre

    Subang Jaya, Selangor, 47500

Other trials in Malaysia

Singapore2 sites

  • National Cancer Center

    Singapore, 169608

  • Singapore General Hospital

    Singapore, 169608

Other trials in Singapore

South Korea1 site

  • Samsung Medical Centre

    Seoul, Seoul, 135-710

Other trials in South Korea

About this study

Official title: An Open-label Phase 2 Study of Intravenous Bortezomib and Oral Panobinostat (LBH589) in Adult Patients With Relapsed/Refractory Peripheral T-cell Lymphoma or NK/T-cell Lymphoma After Failure of Conventional Chemotherapy

The purpose of this study is to determine whether intravenous Bortezomib combined with oral Panobinostat (LBH589) are effective in treating adult patients with relapsed/refractory peripheral T-cell lymphoma or NK/T-cell lymphoma after the failure of conventional chemotherapy.

Read the detailed description

Peripheral T-cell lymphoma (PTCL) and NK/T-cell lymphoma are uncommon diseases that are prevalent in Asia. They are associated with poor prognosis when treated with conventional chemotherapeutic regimes. Their long term disease-free survivals are dismal with only 10-30% of patients surviving long term. More intensive regimens including high dose chemotherapy with autologous stem cell transplant have been tried as primary induction treatment, but have not been shown to be beneficial. Given the rarity of PTCL and NK/T-cell lymphoma, much of the literature consists of studies with small sample size and anecdotal case reports. Therefore, no consensus exists on the best therapeutic strategy for either newly diagnosed or relapsed disease. The failure of conventional chemotherapy in this regard suggests that novel therapies including epigenetic approaches and proteasome inhibition should be explored.

Preclinical data of bortezomib and histone deacetylase inhibitors (HDIs) in T-cell and NK/T-cell lymphoma cell lines are encouraging. Bortezomib and HDIs have also separately demonstrated activity in T and NK/T-cell lymphomas in phase II studies, leading to their separate developments in phase III studies. Demonstration of synergism in these 2 agents, in part due to their dependence on overlapping pathways, suggests that they should be explored as a combination, especially when treating a disease with a very unfavourable outcome. The purpose of this phase II study is to assess the efficacy of orally-administered panobinostat, a potent class I/II pan-deacetylase inhibitor with intravenous bortezomib in this patient population.

Being tested
panobinostat and bortezomib
Keywords
t-cell lymphoma, peripheral t-cell lymphoma, nk/t-cell lymphoma, nasal type, bortezomib, velcade, panobinostat, LBH589b, histone deacetylase inhibitor, proteasome inhibitor
Medical subject headings
Lymphoma, T-Cell, Immunoblastic Lymphadenopathy, Lymphoma, Extranodal NK-T-Cell, Enteropathy-Associated T-Cell Lymphoma, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell, Peripheral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • panobinostat and bortezomibDrug

    Also called LBH589B, Velcade

    oral panobinostat 30 mg 3 times per week AND intravenous bortezomib 1.3mg/m2 on days 1,4,8,11 per cycle

Study groups in NCT00901147
Study groupRoleWhat they receive
panobinostat and bortezomibExperimentalOral Panobinostat and intravenous bortezomib
Receives: Drug: panobinostat and bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    Measured: 1 year

Secondary outcomes (1)

  1. Time to response, Duration of response, Progression-free survival, Overall survival, Safety and tolerability, Changes in disease-related symptoms and ECOG performance status.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionJan 2014
  4. Study completionJan 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00901147
Sponsor's protocol ID
SGH651
Other IDs
SHF/CTG023/2008
Status last verified
Jun 2014
First submitted
11 May 2009
Last updated
27 Jun 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Tan D, Phipps C, Hwang WY, Tan SY, Yeap CH, Chan YH, Tay K, Lim ST, Lee YS, Kumar SG, Ng SC, Fadilah S, Kim WS, Goh YT; SGH651 Investigators. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. Lancet Haematol. 2015 Aug;2(8):e326-33. doi: 10.1016/S2352-3026(15)00097-6. Epub 2015 Jul 7.

    PubMed 26688485

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing panobinostat and bortezomib in people with Peripheral T-cell Lymphoma (Not Otherwise Specified) and Angioimmunoblastic T-cell Lymphoma, run by Singapore General Hospital at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Malaysia, Singapore, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00901147, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2014.

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