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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00901147
Recruitment Status : Completed
First Posted : May 13, 2009
Last Update Posted : June 27, 2014
Information provided by (Responsible Party):
Singapore General Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
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 Drug: panobinostat and bortezomib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : November 2009
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Arm Intervention/treatment
Experimental: panobinostat and bortezomib
Oral Panobinostat and intravenous bortezomib
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
Other Names:
  • LBH589B
  • Velcade

Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Time to response, Duration of response, Progression-free survival, Overall survival, Safety and tolerability, Changes in disease-related symptoms and ECOG performance status. [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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);
    • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00901147

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Korea, Republic of
Samsung Medical Centre
Seoul, Korea, Republic of, 135-710
Subang Jaya Medical Centre
Subang Jaya, Selangor, Malaysia, 47500
Hospital Universiti Kebangsaan Malaysia ( HUKM )
Kuala Lumpur, Malaysia, 56000
National Cancer Center
Singapore, Singapore, 169608
Singapore General Hospital
Singapore, Singapore, 169608
Sponsors and Collaborators
Singapore General Hospital
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Principal Investigator: Yeow Tee Goh, MBBS MMed Singapore General Hospital
Study Chair: Darryl Tan, MBBS MMED Singapore General Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Singapore General Hospital Identifier: NCT00901147     History of Changes
Other Study ID Numbers: SGH651
First Posted: May 13, 2009    Key Record Dates
Last Update Posted: June 27, 2014
Last Verified: June 2014
Keywords provided by Singapore General Hospital:
t-cell lymphoma
peripheral t-cell lymphoma
nk/t-cell lymphoma, nasal type
histone deacetylase inhibitor
proteasome inhibitor
Additional relevant MeSH terms:
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Lymphoma, T-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Lymphoma, Extranodal NK-T-Cell
Enteropathy-Associated T-Cell Lymphoma
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action