search
Back to results

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

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Ibrutinib
Rituximab
Cyclophosphamide
Doxorubicin
vincristine
Prednisolone
Sponsored by
Samsung Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Samsung Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ibrutinib in combination with r-CHOP

Arm Description

Ibrutinib560 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

Outcomes

Primary Outcome Measures

complete response rate
To assess the efficacy of disease control including complete response (CR), partial response (PR) and stable disease (SD)

Secondary Outcome Measures

Progression-free survival
It is a measure of the period of survival without disease progression
Overall survival (OS)
It measures the time from start of treatment to death.
Toxicity Profile
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.

Full Information

First Posted
January 28, 2016
Last Updated
October 19, 2020
Sponsor
Samsung Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT02670616
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 1, 2016 (Actual)
Primary Completion Date
June 2020 (Actual)
Study Completion Date
October 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ibrutinib in combination with r-CHOP
Arm Type
Experimental
Arm Description
Ibrutinib560 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
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
Imbruvica
Intervention Description
560 mg by mouth daily on day 1-21 per each cycle
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Mabthera
Intervention Description
375 mg/m2 IV, day 1
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Endoxan
Intervention Description
750 mg/m2 IV day 1
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
50 mg/m2 IV day 1
Intervention Type
Drug
Intervention Name(s)
vincristine
Intervention Description
1.4 mg/m2 IV on day 1
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Other Intervention Name(s)
solondo
Intervention Description
100mg per day on day 1-5
Primary Outcome Measure Information:
Title
complete response rate
Description
To assess the efficacy of disease control including complete response (CR), partial response (PR) and stable disease (SD)
Time Frame
From date of enrollment until the date first documented disease progression or unacceptable toxicity, whichever came first, assessed up to 48 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
It is a measure of the period of survival without disease progression
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
Title
Overall survival (OS)
Description
It measures the time from start of treatment to death.
Time Frame
Time between the start of treatment and the date of death.assessed up to 48 months
Title
Toxicity Profile
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.
Time Frame
from the date of informed consent signature to 30 days after last drug administration.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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) 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 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 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. 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. At least one measurable lesion ECOG PS 0-2 Informed consent Age ≥ 19 years Exclusion Criteria: 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 History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease or secondary CNS involvement on CT or MRI scan. Pregnancy or breastfeeding Major surgery within 4 weeks of enrollment History of stroke or intracranial hemorrhage within 6 months prior to enrollment Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon). Requires treatment with strong CYP3A inhibitors. 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. Vaccinated with live, attenuated vaccines within 4 weeks of enrollment. 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Won seog KIM, MD,Ph.D.
Organizational Affiliation
Samsung Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
State/Province
Seoul, Gangnam-gu
ZIP/Postal Code
135-710
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs