Bortezomib Maintenance in High Risk DLBCL

Study Overview
=================
Brief Summary
-----------------
This study is an Open-labeled, multicenter Phase II study of Bortezomib for maintenance therapy in patients with high risk diffuse large B cell lymphoma (DLBCL). Primary objective is 3 years relapse free survival (RFS) and Secondary objectives are 3 years overall survival (OS), 3 years event free survival (EFS),Toxicities profiles, Quality of Life (FACT&GOG-Ntx)

Detailed Description
-----------------
High-intermediate or high risk in IPI has a long-term chance of cure in the range about 50% in patients with DLBCL treated by R-CHOP. These high risk patients should be considered for additional new treatment to standard R-CHOP or investigational approaches in the context of clinical trials that are designed to ensure that potentially curative therapy. Bortezomib has shown activity in vitro against DLBCL-derived cell lines. Single-agent bortezomib or chemotherapy combined bortezomib are feasible in follicular, mantle cell, marginal zone lymphoma and DLBCL with manageable toxicities. Bortezomib enhances the activity of chemotherapy in non-GCB but not GCB DLBCL, and provide a rational therapeutic approach based on genetically distinct DLBCL subtypes. High CR/CRu rate with bortezomib with standard R-CHOP suggests it may be a good backbone for additional maintenance leading to durable response. However, there is no study of bortezomib as maintenance therapy after treated with R-CHOP in high risk patients with DLBCL. So we applied additional bortezomib as maintenance therapy in order to assess improving efficacy and survival rates in high risk patients with non-GCB DLBCL who had been confirmed CR after treated with R-CHOP.

Official Title
-----------------
Open-label, Multicenter Phase II Study of Bortezomib for Maintenance Therapy in Patients With High Risk Diffuse Large B Cell Lymphoma

Conditions
-----------------
Diffuse Large B Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Bortezomib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly histologically confirmed CD20 positive diffuse large B-cell lymphomas and only Non-GCB type will be included High intermediate or high risk by IPI risk, or Bulky mass ≥ 10cm at diagnosis Complete response is confirmed after six or eight cycles R-CHOP chemotherapy by CT scan with confirmed negative PET-CT based on the Revised International Workshop Criteria. Additional surgery or radiotherapy are accepted Age ≥ 20 Performance status (ECOG) ≤ 2 Adeqaute renal function: Cr < 2.5 mg/dL Adeqaute liver functions: Transaminase (AST/ALT) < 3 x upper normal value UNV)Bilirubin < 1.5 x UNV Alkaline phosphatase < 5 xUNV Adeqaute BM functions: ANC > 1,000/uL and platelet > 75,000/uL and hemoglobin > 9.0 g/dL Written Informed consent Exclusion Criteria: Tumor response after 6-8 cycles CTx< CR Consider stem cell transplantation Central nervous system (CNS) metastases Pregnant or lactating women, patients of childbearing potential not employing adequate contraception Other serious illness or medical conditions A. Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry B. History of significant neurologic or psychiatric disorders including dementia or seizures C. Active uncontrolled infection Any other malignancies within the past 5 years except curatively treated non- melanoma skin cancer or in situ carcinoma of cervix uteri. Prior history of allegic reaction to study treatment drugs Peripheral neuropathy grade 2 or worse DLBCL of the testis and primary mediastinal DLBCL

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib<br>bortezomib 1.3mg/m2 subcutaneous on day 1 and15 | Drug: Bortezomib<br>* Bortezomib 1.3mg/m2, on day 1 and 15 SC Repeat every month for 12months<br>* Other names: velcade;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3years relapse free survival | 3years relapse free survival will be assessed after starting maintenance therapy for 1year and then following up for 3years. | from the date of first drug administration until the date of last follow up, assessed up to 4years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3years overall survival | 3years overall survival will be assessed after starting maintenance therapy for 1year and then following up for 3years. | from the date of first drug administration until the date of last follow up, assessed up to 4years | 
| 3years event free survival | 3years event free survival will be assessed after starting maintenance therapy for 1year and then following up for 3years. | from the date of first drug administration until the date of last follow up, assessed up to 4years | 
| Toxicity profiles | Safety profiles will be evaluated using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | from the date of first drug administration until the date of the 30th day after last cycle of chemotherapy | 
| Quality of life scale | Quality of life will be assessed after starting maintenance therapy for 1year and then following up for 3years by using FACT&GOG-Ntx. | from the date of first drug administration until the date of last follow up, assessed up to 4years |