A Phase II Study of Ibrutinib, Rituximab and mini-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy in very elderly patients with newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)
- Conditions
- elderly DLBCLCancer - Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
- Registration Number
- ACTRN12615000551594
- Lead Sponsor
- Australasian Leukaemia and Lymphoma Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 80
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method