A Phase II Study of Ibrutinib, Rituximab and mini-CHOP therapy in very elderly patients with newly diagnosed DLBCL (NHL29)

Funding

Commercial sector/Industry,Janssen-Cilag Pty Ltd

Scientific enquiries

Prof Judith Trotman

Brief Summary

The study will evaluate the deliverability and efficacy of Ibrutinib-R-mini-CHOP chemotherapy in elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Who is it for? You may be eligible to join this study if you are aged 75 years or above and have been newly diagnosed with DLBCL for which you have received no prior treatment (excluding prednisone). Study details All participants in this study will be treated with a chemotherapy regime known as Ibrutinib-R-mini-CHOP. This w .... The study will evaluate the deliverability and efficacy of Ibrutinib-R-mini-CHOP chemotherapy in elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Who is it for? You may be eligible to join this study if you are aged 75 years or above and have been newly diagnosed with DLBCL for which you have received no prior treatment (excluding prednisone). Study details All participants in this study will be treated with a chemotherapy regime known as Ibrutinib-R-mini-CHOP. This will include treatment with the drugs prednisone (orally), ibrutinib (orally), rituximab intravenously ((IV) - i.e. administered directly into the vein), cyclophosphamide IV, doxorubicin IV, vincristine IV and Pegfilgrastim G-CSF (subcutaneous injection). Treatment duration will be for up to 8 x 28 day cycles as tolerated. All participants will be regularly assessed for a minimum of 2 years in order to evaluate the safety, toxicity and effectiveness of treatment.
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Key Inclusion Criteria

1. Subject must be 75 years of age or older 2. No prior treatment for DLBCL excluding prednisone 3. Histologically confirmed de novo CD20+ DLBCL 4. Stage I bulky (largest dimension of lesion >/= 6cm), II, III or IV disease by the Ann Arbor Classification 5. At least 1 measurable site of disease according to the 2014 Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma – the Lugano Classification. The site of disease must be greater than 1.5 .... 1. Subject must be 75 years of age or older 2. No prior treatment for DLBCL excluding prednisone 3. Histologically confirmed de novo CD20+ DLBCL 4. Stage I bulky (largest dimension of lesion >/= 6cm), II, III or IV disease by the Ann Arbor Classification 5. At least 1 measurable site of disease according to the 2014 Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma – the Lugano Classification. The site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement. An extranodal lesion should have a longest diameter of > 1cm. 6. Eastern Cooperative Oncology Group performance status score of 0, 1, or 2 (this can be as measured after any pre-phase prednisone) 7. LVEF within institutional normal limits, as determined by Gated Heart Pool Scan, or if not available, echocardiogram 8. Minimum life expectancy of 3 months 9. Haematology values must be within the following limits: a. Absolute neutrophil count (ANC) >=1.0 x10^9/Lindependent of growth factor support b. Platelets >=100x10^9/L or >=50x10^9/L if bone marrow involvement independent of transfusion support in either situation 10. Biochemical values within the following limits: a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3 x upper limit of normal (ULN) b. Total bilirubin <= 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin c. Creatinine Clearance (as measured by Cockroft Gault) >/= 40 mL/min/1.73m2 11. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. 12. 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.
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Key Exclusion Criteria

1. History of treated lymphoma of any subtype 2. CNS or meningeal involvement 3. Contraindication to any drug in the chemotherapy regimen 4. Serious active co-morbid disease according to the investigator’s decision 5. Poor renal function, defined as a Creatinine Clearance Rate (as measured by Cockcroft Gault) < 40 mL/min/1.73m2 6. Poor hepatic function, defined as Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) and/or total bilirubin > 1.5 x .... 1. History of treated lymphoma of any subtype 2. CNS or meningeal involvement 3. Contraindication to any drug in the chemotherapy regimen 4. Serious active co-morbid disease according to the investigator’s decision 5. Poor renal function, defined as a Creatinine Clearance Rate (as measured by Cockcroft Gault) < 40 mL/min/1.73m2 6. Poor hepatic function, defined as Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) and/or total bilirubin > 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin 7. Poor bone-marrow reserve, defined as absolute neutrophil count (ANC) < 1.0x10^9/L independent of growth factor support and/or platelet count < 100x10^9/L or < 50x10^9/L if bone marrow involvement independent of transfusion support in either situation 8. History of malignancy during the past 3 years, with the exception of non-melanoma skin cancers or stage 0 (in situ) carcinoma. 9. Treatment with any investigational drug within 30 days before the planned first cycle of chemotherapy 10. Requires anticoagulation with warfarin or equivalent vitamin K antagonists 11. Requires dual antiplatelet therapy with aspirin and a P2Y12 antagonist 12. Requires treatment with strong CYP3A inhibitors 13. Requires treatment with fish oil 14. Prior anthracycline use >= 150 mg/m2 15. History of stroke or intracranial haemorrhage within 6 months of enrolment 16. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction 17. Known bleeding disorders (e.g. von Willebrand’s disease) 18. Major surgery within 4 weeks of enrolment 19. 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 20. 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 21. Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus (HCV; RNA polymerase chain reaction [PCR]-positive) or active Hepatitis B Virus (HBV; DNA PCR-positive) infection. Only patients who are HBV surface antigen (HBVsAg) and/or HBV core antibody (HBVcAb) positive are required to undergo HBV DNA PCR testing. Subjects with PCR-negative HBV or who are HBV core antibody positive are permitted in the study but must be on HBV prophylaxis. 22. Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. 23. Vaccinated with live, attenuated vaccines within 4 weeks of enrolment.
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