Clinical Trials /

Study of Ibrutinib in Combination With Rituximab-CHOP in Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma

NCT02670616

Description:

This study was conducted to evaluate the complete response rate of Ibrutinib + R-CHOP in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Ibrutinib in Combination With Rituximab-CHOP in Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma
  • Official Title: Phase II Study of Ibrutinib in Combination With Rituximab-CHOP in Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma 54179060LYM2003 (Nick Name: IVORY Study)

Clinical Trial IDs

  • ORG STUDY ID: 2015-04-027
  • NCT ID: NCT02670616

Conditions

  • Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
IbrutinibImbruvicaibrutinib in combination with r-CHOP
RituximabMabtheraibrutinib in combination with r-CHOP
CyclophosphamideEndoxanibrutinib in combination with r-CHOP
DoxorubicinAdriamycinibrutinib in combination with r-CHOP
vincristineibrutinib in combination with r-CHOP
Prednisolonesolondoibrutinib in combination with r-CHOP

Purpose

This study was conducted to evaluate the complete response rate of Ibrutinib + R-CHOP in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Detailed Description

      EBV-positive diffuse large B-cell lymphoma has EBV-mediated carcinogenic signaling pathway
      activation, and this diverse intracellular pathway may be a potential therapeutic target in
      this disease.

      The BTK inhibitor, ibrutinib, targets the B cell receptor signaling pathway and is active
      against B cell non-Hodgkin lymphoma. As a result, evidence of the antitumor effect of
      ibrutinib has been accumulated in some B-cell lymphoma forms such as mantle cell lymphoma.
      The addition of ibrutinib to standard chemotherapy, rituximab-CHOP, is considered to be an
      effective treatment for patients with EBV-positive diffuse large B-cell lymphomas, because it
      is known to show a poor response to treatment compared to (NOS) diffuse large B- It can
      provide benefits to patients.

      The BTK inhibitor, ibrutinib, targets the B cell receptor signaling pathway and is active
      against B cell non-Hodgkin lymphoma. As a result, evidence of the antitumor effect of
      ibrutinib has been accumulated in some B-cell lymphoma forms such as mantle cell lymphoma.
      The addition of ibrutinib to standard chemotherapy, rituximab-CHOP, is considered to be an
      effective treatment for patients with EBV-positive diffuse large B-cell lymphomas, because it
      is known to show a poor response to treatment compared to (NOS) diffuse large B- It can
      provide benefits to patients.
    

Trial Arms

NameTypeDescriptionInterventions
ibrutinib in combination with r-CHOPExperimentalIbrutinib560 mg daily on day 1-21 per each cycle ,Rituximab375 mg/m2, Cyclophosphamide750 mg/m2, doxorubicin 50 mg/m2, vincristine1.4 mg/m2 on day 1; Prednisolone 100mg per day on day 1-5 ,cycle length: 21 days ,Six cycles of treatment
  • Ibrutinib
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • vincristine
  • Prednisolone

Eligibility Criteria

        Inclusion Criteria:

          1. Newly diagnosed, histologically proven EBV-positive Diffuse large B-cell lymphoma
             A.EBV positivity: The presence of EBER-positive tumor cells ≥ 20% B.DLBCL based on the
             WHO classification 2008

          2. Hematology values must be within the following limits:

             A.Absolute neutrophil count 1000/mm3 independent of growth factor support B.Platelets
             100,000/mm3 or 50,000/mm3 if bone marrow involvement independent of transfusion
             support in either situation C.Hemoglobin ≥ 10.0 g/dL (may be transfused or
             erythropoietin treated)

          3. Biochemical values within the following limits:

             A.Alanine aminotransferase and aspartate aminotransferase≤ 3 x upper limit of normal
             B.Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of
             non-hepatic origin C.Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration
             Rate (Cockroft Gault) ≥ 40 mL/min/1.73m2 D.Serum calcium ≤ 12.0 mg/dL

          4. Women of childbearing potential and men who are sexually active must be practicing a
             highly effective method of birth control during and after the study consistent with
             local regulations regarding the use of birth control methods for subjects
             participating in clinical trials. Men must agree to not donate sperm during and after
             the study. For females, these restrictions apply for 1 month after the last dose of
             study drug. For males, these restrictions apply for 3 months after the last dose of
             study drug

          5. Women of childbearing potential must have a negative serum (beta-human chorionic
             gonadotropin)or urine pregnancy test at Screening. Women who are pregnant or
             breastfeeding are ineligible for this study.

          6. Sign (or their legally-acceptable representatives must sign) an informed consent
             document indicating that they understand the purpose of and procedures required for
             the study, including biomarkers, and are willing to participate in the study.

          7. At least one measurable lesion

          8. ECOG PS 0-2

          9. Informed consent

         10. Age ≥ 19 years

        Exclusion Criteria:

          1. Previous treatment history for EBV-positive DLBCL including any kinds of chemotherapy

             •Exception: a) Prednisolone 100mg or equivalent dosage of any types of steroid is
             allowed (Maximum 7 days); b) Radiation for reducing symptom related with mass effect
             is allowed

          2. History of or known carcinomatous meningitis, or evidence of symptomatic
             leptomeningeal disease or secondary CNS involvement on CT or MRI scan.

          3. Pregnancy or breastfeeding

          4. Major surgery within 4 weeks of enrollment

          5. History of stroke or intracranial hemorrhage within 6 months prior to enrollment

          6. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg,
             phenprocoumon).

          7. Requires treatment with strong CYP3A inhibitors.

          8. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
             Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
             the New York Heart Association Functional Classification.

          9. Vaccinated with live, attenuated vaccines within 4 weeks of enrollment.

         10. Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or
             active Hepatitis B Virus infection or any uncontrolled active systemic infection
             requiring intravenous (IV) antibiotics.

         11. Any life-threatening illness, medical condition, or organ system dysfunction which, in
             the investigator's opinion, could compromise the subject's safety, interfere with the
             absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue
             risk.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:complete response rate
Time Frame:From date of enrollment until the date first documented disease progression or unacceptable toxicity, whichever came first, assessed up to 48 months
Safety Issue:
Description:To assess the efficacy of disease control including complete response (CR), partial response (PR) and stable disease (SD)

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:the time between the date of treatment start and the date of death due to any cause or date of disease progression..assessed up to 48 months
Safety Issue:
Description:It is a measure of the period of survival without disease progression
Measure:Overall survival (OS)
Time Frame:Time between the start of treatment and the date of death.assessed up to 48 months
Safety Issue:
Description:It measures the time from start of treatment to death.
Measure:Toxicity Profile
Time Frame:from the date of informed consent signature to 30 days after last drug administration.
Safety Issue:
Description:Clinical and laboratory toxicity/symptomatology will be graded based on the NCIC CTG v4.03. Adverse events not reported in NCIC CTG will be categorized into mild, moderate, severe, and fatal and further classified to CTCAE Grades 1-4.

Details

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

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