Beschreibung

Ibrutinib and standard immuno-therapy R-CHOEP-14 in younger, high risk patients with diffuse large B-cell lymphoma

Studienstatus

Rekrutierungsziel erreicht/keine neuen Patienten

Allgemeine Infos zum Antrag

The primary objective is to estimate the 2-year progression-free survival (PFS) achieved with ibrutinib in combination with immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (R-CHOEP) in younger, high-risk patients.

The secondary objectives for efficacy are to evaluate overall survival (OS), event-free survival (EFS), rate of complete remission (CR), rate of partial remission (PR), overall response rate (ORR) (CR+PR), progression rate, relapse rate and the duration of response.
Other secondary objectives of the trial are to assess the
• rate of treatment-related deaths,
• feasibility, safety, toxicity, and protocol adherence of ibrutinib when combined with R-CHOEP and
• outcome according to biological parameters of the tumor.

Patients with primary diagnosis of DLBCL aged 18 - 60 years and aaIPI 2 or 3.

75 patients with DLBCL

2-year PFS with 95% confidence intervals (CI) in 75 patients without CNS disease.

Secondary endpoints for efficacy:
OS, EFS, CR rate, PR rate, ORR, progression rate, relapse rate, duration of response.
Other secondary endpoints:
AEs, SAEs, treatment-related deaths, Secondary malignancies,
Number and duration of therapy cycles, Cumulative doses of cyclophosphamide, doxorubicin, vincristine, etoposide, rituximab and ibrutinib, outcome according to biological parameters.

Spezifische Infos zum Antrag

1. 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.
2. Age between 18-60 years
3. Risk score 2 or 3 according to aaIPI
4. Histology: Primary diagnosis of
- DLBCL (NOS) or
- High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements or
- High-grade B-cell lymphoma, NOS
5. Performance status: ECOG 0-3
6. Stage: all stages according Ann Arbor
7. ANC: > 1000 cells/microliter (independent of growth factor support)
8. Platelet count ? 100.000/mm3 or ? 50.000/mm3 if bone marrow involvement independent of transfusion support in either situation.
9. ALT and AST: < 3 x ULN
10. Total Bilirubin: < 1.5 x ULN
11. Serum Creatinine: < 2 x ULN or estimated GFR (GFR [Cockcroft-Gault]) ? 40 ml/min
12. 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.
13. 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.
14. Willing/ able to adhere to the prohibitions and restrictions specified in this protocol.

1. Vaccinated with live, attenuated vaccines within 4 weeks of inclusion.
2. Major surgery within 4 weeks of inclusion.
3. Any prior lymphoma-directed therapy (except pre-phase treatment).
4. Known central nervous system involvement.
5. Diagnosed or treated for malignancy other than DLBCL, in particular any other (indolent) lymphoma.
6. 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.
7. Bone marrow involvement > 25%
8. History of stroke or intracranial hemorrhage within six months of inclusion.
9. Requires anticoagulation with warfarin or equivalent vitamin K antagonist.
10. 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.
11. Requires treatment with strong CYP3A inhibitors.
12. Use of preparations containing St. John’s Wort.
13. 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.
14. Concurrent treatment with other investigational agent or X-ray therapy.
15. Previous chemo- or radiotherapy for any other malignancy, in particular indolent lymphoma.
16. 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.
17. Participation in another interventional clinical trial during this trial. There may be exceptions at the discretion of the coordinating investigator.

First patient in: February 2018
Last patient in: February 2020
Follow up ends: February 2022

12

Nein

• Synopse R-CHOEP-brut