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

NCT02670616 | Completed Phase 2 DMC

• 1 other identifier: 2015-04-027
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• complete response rate

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

  From date of enrollment until the date first documented disease progression or unacceptable toxicity, whichever came first, assessed up to 48 months

Secondary Outcomes (3)

• Progression-free survival

  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

• Overall survival (OS)

  Time between the start of treatment and the date of death.assessed up to 48 months

• Toxicity Profile

  from the date of informed consent signature to 30 days after last drug administration.

Study Arms (1)

ibrutinib in combination with r-CHOP

EXPERIMENTAL

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

Drug: Ibrutinib; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: vincristine; Drug: Prednisolone

Interventions

Ibrutinib DRUG

560 mg by mouth daily on day 1-21 per each cycle

Also known as: Imbruvica

ibrutinib in combination with r-CHOP

Rituximab DRUG

375 mg/m2 IV, day 1

Also known as: Mabthera

ibrutinib in combination with r-CHOP

Cyclophosphamide DRUG

750 mg/m2 IV day 1

Also known as: Endoxan

ibrutinib in combination with r-CHOP

Doxorubicin DRUG

50 mg/m2 IV day 1

Also known as: Adriamycin

ibrutinib in combination with r-CHOP

vincristine DRUG

1.4 mg/m2 IV on day 1

ibrutinib in combination with r-CHOP

Prednisolone DRUG

100mg per day on day 1-5

Also known as: solondo

ibrutinib in combination with r-CHOP

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, Seoul, Gangnam-gu, 135-710, South Korea

Location

MeSH Terms

Interventions

ibrutinib; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisolone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Won seog KIM, MD,Ph.D.

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 2, 2016
• Study Start: May 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: October 1, 2020
• Last Updated: October 22, 2020

Record last verified: 2020-10

Locations

KR (1)