Ibrutinib and Standard Immuno-Chemotherapy in Younger, High-Risk Patients With Diffuse Large B-Cell Lymphoma

NCT03399513 | Completed Phase 2 DMC

• 1 other identifier: UKM17_0017
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 12

Brief Summary

This study will investigate if treatment results obtained with R-CHOEP in young high-risk patients with diffuse large B-cell lymphoma can be further improved by the addition of ibrutinib to this regimen.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Ibrutinib

Outcome Measures

Primary Outcomes (1)

• 2-year progression-free survival

  Length of time that a patient lives without disease progression or relapse.

  From the day of inclusion into the study until one of the following events occurs, whichever is first: disease progression, relapse, death due to any other cause (assessed up to 4 years).

Secondary Outcomes (14)

• Overall survival

  From the day of inclusion into the study to death due to any cause (assessed up to 4 years).

• Event-free survival

  From the day of inclusion into the study until one of the following events occurs, whichever comes first: disease progression, start of additional, unplanned anti-tumor therapy, relapse, death due to any other cause (assessed up to 4 years).

• Rate of complete remission

  From the day of inclusion into the study until date of complete remission (assessed up to 6 months).

• Rate of partial remission

  From the day of inclusion into the study until date of partial remission (assessed up to 6 months).

• Overall response rate

  From the day of inclusion into the study until date of complete or partial remission (assessed up to 6 months).

Study Arms (1)

Ibrutinib and R-CHOEP chemotherapy

EXPERIMENTAL

All patients will receive 8 cycles of R-CHOEP immunochemotherapy every two weeks with the following doses per cycle: rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m² (dose capped at 2 mg), etoposide 300 mg/m², prednisolone 500 mg. In addition, ibrutinib capsules will be administered orally once daily at a dose of 560 mg (4 x 140 mg hard capsules) for 112 days.

Drug: Ibrutinib Oral Capsule [Imbruvica]; Drug: R-CHOEP chemotherapy

Interventions

Ibrutinib Oral Capsule [Imbruvica] DRUG

Imbruvica 140 mg hard capsules (Active substance: Ibrutinib)

Ibrutinib and R-CHOEP chemotherapy

R-CHOEP chemotherapy DRUG

Immunochemotherapy

Ibrutinib and R-CHOEP chemotherapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Age between 18-60 years
• Risk score 2 or 3 according to age-adjusted International Prognostic Index
• Histology: Primary diagnosis of diffuse large B-cell lymphoma
• Performance status: ECOG (toxicity and response criteria of the eastern cooperative oncology group) 0-3
• Stage: all stages according Ann Arbor
• Absolute neutrophil count: \> 1000 cells/microliter (independent of growth factor support)
• Platelet count ≥ 100.000/mm³ or ≥ 50.000/mm³ if bone marrow involvement independent of transfusion support in either situation.
• Alanine-aminotransferase and Aspartate-aminotransferase: \< 3 x Upper limit of normal value
• Total Bilirubin: \< 1.5 x Upper limit of normal value
• Serum Creatinine: \< 2 x Upper limit of normal value or estimated Glomerular filtration rate (Glomerular filtration rate \[Cockcroft-Gault\]) ≥ 40 ml/min
• Women of childbearing potential and men who are sexually active must be practising 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 male subjects, these restrictions apply for 6 months after last dose of study drug. For female subjects, they apply for 12 months after last dose of study drug.
• Women of childbearing potential must have negative serum or urine beta-human chorionic gonadotropin pregnancy test at screening. Women who are pregnant or breast-feeding are ineligible for this study.
• Willing/ able to adhere to the prohibitions and restrictions specified in this protocol.

You may not qualify if:

• Any prior lymphoma-directed therapy (except pre-phase treatment).
• Known central nervous system involvement.
• Diagnosed or treated for malignancy other than diffuse large B-cell lymphoma, in particular any other (indolent) lymphoma.
• 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 or 4 cardiac disease as defined by the New York Heart Association Functional classification.
• Bone marrow involvement \> 25%
• Requires anticoagulation with warfarin or equivalent vitamin K antagonist.
• Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring IV antibiotics.
• Requires treatment with strong CYP3A inhibitors.
• Use of preparations containing St. John's Wort.
• 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.
• Concurrent treatment with other investigational agent or X-ray therapy.
• Previous chemo- or radiotherapy for any other malignancy, in particular indolent lymphoma.
• Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, to give informed consent or to comply with the study protocol.
• Participation in another interventional clinical trial during this trial. There may be exceptions at the discretion of the coordinating investigator.

Sponsors & Collaborators

• University Hospital Muenster: lead
• Janssen-Cilag G.m.b.H: collaborator

Study Sites (12)

HELIOS Hospital Berlin-Buch

Berlin, 13125, Germany

Location

Hospital Chemnitz

Chemnitz, 09116, Germany

Location

University Hospital Cologne

Cologne, 50937, Germany

Location

University Hospital Göttingen

Göttingen, 37075, Germany

Location

University Hospital Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

University Hospital Heidelberg

Heidelberg, 69120, Germany

Location

Saarland University Hospital

Homburg, 66421, Germany

Location

Johannes Wesling Hospital Minden

Minden, 32429, Germany

Location

University Hospital Muenster

Münster, 48149, Germany

Location

Rostock University Medical Center

Rostock, 18057, Germany

Location

University Hospital Tuebingen

Tübingen, 72076, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Prof. Norbert Schmitz, MD

  University Hospital Muenster

  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: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: January 16, 2018
• Study Start: May 3, 2018
• Primary Completion: December 23, 2023
• Study Completion: December 23, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Locations

DE (12)