OBJECTIVES of the Study:Primary ObjectiveTo evaluate if the addition of ibrutinib to R-CHOP prolongs event-free survival (EFS) compared withR-CHOP alone in subjects with newly diagnosed non-GCB DLBCL.Secondary ObjectivesTo compare ibrutinib in…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective
To evaluate if the addition of ibrutinib to R-CHOP prolongs event-free survival
(EFS) compared with
R-CHOP alone in subjects with newly diagnosed non-GCB DLBCL.
Secondary outcome
Secondary Objectives
To compare ibrutinib in combination with R-CHOP versus R-CHOP alone with regard
to progression-free
survival (PFS), overall survival, complete response [CR] rate, patient-reported
lymphoma symptoms and
concerns, treatment benefit of ibrutinib in subjects with the ABC subtype based
on gene expression
profiling (GEP), and safety. Additional secondary objectives are to
characterize the pharmacokinetics of
ibrutinib and explore the potential relationships between ibrutinib metrics of
exposure with relevant
clinical or biomarker information.
Background summary
Hypothesis:
Ibrutinib in combination with R-CHOP will prolong EFS in subjects with newly
diagnosed
non-GCB DLBCL compared with R-CHOP alone.
Study objective
OBJECTIVES of the Study:
Primary Objective
To evaluate if the addition of ibrutinib to R-CHOP prolongs event-free survival
(EFS) compared with
R-CHOP alone in subjects with newly diagnosed non-GCB DLBCL.
Secondary Objectives
To compare ibrutinib in combination with R-CHOP versus R-CHOP alone with regard
to progression-free
survival (PFS), overall survival, complete response [CR] rate, patient-reported
lymphoma symptoms and
concerns, treatment benefit of ibrutinib in subjects with the ABC subtype based
on gene expression
profiling (GEP), and safety. Additional secondary objectives are to
characterize the pharmacokinetics of
ibrutinib and explore the potential relationships between ibrutinib metrics of
exposure with relevant
clinical or biomarker information.
Study design
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's
Tyrosine Kinase (BTK)
Inhibitor, PCI-32765 (Ibrutinib), in Combination with Rituximab,
Cyclophosphamide, Doxorubicin,
Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed
Non-Germinal Center B-Cell
Subtype of Diffuse Large B-Cell Lymphoma
Intervention
One group of patients will receive daily capsules of Ibrutinib, while the other
group of patients will receive daily placebo capsules
Study burden and risks
Hemorrhagic Adverse Events:
Ibrutinib is known to affect platelet function in vitro; the clinical
significance of this effect is
unknown. There have been reports of subjects having hemorrhagic events,
including subdural
hematomas, while on treatment with study drug. It is difficult to
comprehensively evaluate these
subjects as to whether or not the clinical presentation is attributable to
ibrutinib. Other risk
factors for subdural hematoma may include age, history of fall, and concomitant
use of warfarin.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
- No prior treatment for diffuse B-cell lymphoma (DLBCL) ;- Histologically-confirmed nongerminal center B-cell subtype DLBCL ;- Stage II (not candidates for local x-ray therapy), III, or IV disease by the Ann Arbor Classification ;- At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma ;- Revised International Prognostic Index score of ><=1 ;- Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2 ;- Hematology and biochemical laboratory values within protocol- efined parameters prior to random assignment and at baseline ;- Left ventricular ejection fraction within institutional normal limits, as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan ;- Agrees to protocol-defined use of effective contraception (for women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose of study drug, whichever is later; for men, these restrictions apply for 12 months;after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later) ;- Men must agree to not donate sperm during and after the study for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later ;- Women of childbearing potential must have a negative serum or urine pregnancy test at screening
Exclusion criteria
- Major surgery within 4 weeks of random assignment ;- Known central nervous system or primary mediastinal lymphoma ;- Prior history of indolent lymphoma ;- Diagnosed or treated for malignancy other than DLBCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before random assignment; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease ;- History of stroke or intracranial hemorrhage within 6 months prior to random assignment ;- Requires anticoagulation with warfarin or equivalent vitamin K;antagonists ;- Requires treatment with strong CYP3A inhibitors ;- Prior anthracycline use >=150 mg/m2 ;- 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 ;- Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics ;- Women who are pregnant or breastfeeding ;- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator*s opinion, could compromise the patient*s safety, interfere with the absorption or metabolism of;ibrutinib capsules, or put the study outcomes at undue risk
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000959-40-NL |
| ClinicalTrials.gov | NCT01855750 |
| CCMO | NL45535.018.13 |