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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Singapore General Hospital
ClinicalTrials.gov Identifier:
NCT00901147
First received: May 11, 2009
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Singapore General Hospital:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: November 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00901147

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

No publications provided

Responsible Party: Singapore General Hospital
ClinicalTrials.gov Identifier: NCT00901147     History of Changes
Other Study ID Numbers: SGH651, SHF/CTG023/2008
Study First Received: May 11, 2009
Last Updated: June 26, 2014
Health Authority: Singapore: Health Sciences Authority

Keywords provided by Singapore General Hospital:
t-cell lymphoma
peripheral t-cell lymphoma
nk/t-cell lymphoma, nasal type
bortezomib
velcade
panobinostat
LBH589b
histone deacetylase inhibitor
proteasome inhibitor

Additional relevant MeSH terms:
Immunoblastic Lymphadenopathy
Intestinal Diseases
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Enteropathy-Associated T-Cell Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastrointestinal Diseases
Digestive System Diseases
Neoplasms by Histologic Type
Neoplasms
Bortezomib
Panobinostat
Proteasome Inhibitors
Histone Deacetylase Inhibitors
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014