NCT00901147

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Singapore General Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Peripheral T-cell Lymphoma (Not Otherwise Specified)
• Angioimmunoblastic T-cell Lymphoma
• Extranodal NK/T-cell Lymphoma Nasal Type
• Enteropathy- Type T-cell Lymphoma
• Hepatosplenic T-cell Lymphoma
• Anaplastic Large Cell Lymphoma (ALCL) (ALK-1 Negative)
• Relapsed ALCL (ALK-1 Positive) Post Autologous Transplant

Interventions

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

Timeline

• Start date: 2009-11-01
• Primary completion: 2014-01-01
• Completion: 2014-01-01
• First posted: 2009-05-13
• Last updated: 2014-06-27

Locations

5 sites across 3 countries: Malaysia, Singapore, South Korea