Clinical Trials /

Bortezomib Maintenance in High Risk DLBCL

NCT01965977

Description:

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)

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: SMC2013-04-124
  • NCT ID: NCT01965977

Conditions

  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
BortezomibvelcadeBortezomib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
BortezomibExperimentalbortezomib 1.3mg/m2 subcutaneous on day 1 and15
  • Bortezomib

Eligibility Criteria

        Inclusion Criteria:

          1. Newly histologically confirmed CD20 positive diffuse large B-cell lymphomas and only
             Non-GCB type will be included

          2. High intermediate or high risk by IPI risk, or Bulky mass ≥ 10cm at diagnosis

          3. 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.

          4. Additional surgery or radiotherapy are accepted

          5. Age ≥ 20

          6. Performance status (ECOG) ≤ 2

          7. Adeqaute renal function: Cr < 2.5 mg/dL

          8. Adeqaute liver functions: Transaminase (AST/ALT) < 3 x upper normal value
             UNV)Bilirubin < 1.5 x UNV Alkaline phosphatase < 5 xUNV

          9. Adeqaute BM functions: ANC > 1,000/uL and platelet > 75,000/uL and hemoglobin > 9.0
             g/dL

         10. Written Informed consent

        Exclusion Criteria:

          1. Tumor response after 6-8 cycles CTx< CR

          2. Consider stem cell transplantation

          3. Central nervous system (CNS) metastases

          4. Pregnant or lactating women, patients of childbearing potential not employing adequate
             contraception

          5. 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

          6. Any other malignancies within the past 5 years except curatively treated non- melanoma
             skin cancer or in situ carcinoma of cervix uteri.

          7. Prior history of allegic reaction to study treatment drugs

          8. Peripheral neuropathy grade 2 or worse

          9. DLBCL of the testis and primary mediastinal DLBCL
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Samsung Medical Center

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