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A Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients with Previously Treated Indolent Non-Hodgkin Lymphoma

Conditions
Indolent Non-Hodgkin Lymphoma (iNHL)
MedDRA version: 14.1Level: HLTClassification code 10029621Term: Non-Hodgkin's lymphomas unspecified histology indolentSystem Organ Class: 100000004851
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2013-003093-27-ES
Lead Sponsor
Janssen-Cilag International NV
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
400
Inclusion Criteria

- Histologically confirmed diagnosis of B-cell indolent Non-Hodgkin lymphoma with histological subtype limited to follicular lymphoma or marginal zone lymphoma
- At least 1 prior treatment with a CD20 antibody combination chemotherapy regimen
- Disease that has relapsed or was refractory after prior chemoimmunotherapy
- At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma 2007
- Eastern Cooperative Oncology Group performance status grade 0 or 1
- Laboratory values within protocol-defined parameters
- Agrees to protocol-defined use of effective contraception
- Men must agree not to donate sperm during and after the study for 6 months after the last dose of bendamustine, 12 months after the last dose of rituximab, or 3 months after the last dose of study medication, whichever is later
- Women of childbearing potential must have a negative serum or urine
pregnancy test at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion Criteria

-Prior treatment according to protocol-defined criteria
-Unable to receive background chemotherapy based on prior treatment history and cardiac function
-Known central nervous system lymphoma
-Diagnosed or treated for malignancy other than indolent Non-Hodgkin lymphoma
-History of stroke or intracranial hemorrhage within 6 months prior to randomization
-Requires anticoagulation with warfarin or equivalent Vitamin K antagonists or treatment with strong CYP3A4/5 inhibitors
-Clinically significant cardiovascular disease
-Known history of human immunodeficiency virus or active infection with hepatitis C or B or any uncontrolled active systemic infection requiring intravenous antibiotics
-Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator?s opinion, could compromise the participant?s safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
-Women who are pregnant or breastfeeding

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: The primary objective of this study is to evaluate whether the addition of ibrutinib to bendamustine and rituximab (BR) combination or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination will result in prolongation of PFS compared with either BR or R-CHOP alone in subjects with previously treated iNHL (FL or MZL).;Secondary Objective: The secondary objectives are to compare treatment groups in terms of the following:<br>? overall survival (OS)<br>? complete response rate (CR)<br>? overall response rate ORR (CR+PR)<br>? duration of response (DOR)<br>? patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)<br>? safety of ibrutinib when combined with BR or R-CHOP;Primary end point(s): Progression-free survival;Timepoint(s) of evaluation of this end point: Up to approximately 7 years after the first participant is randomized
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Overall survival<br>1/ Overall survival<br>2/ Complete response rate<br>3/ Overall response rate<br>4/ Duration of response<br>5/ Participants with change in patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)<br>6/ Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT);Timepoint(s) of evaluation of this end point: 1/ Up to approximately 7 years after the first participant is randomized<br>2/ Up to approximately 7 years after the first participant is randomized<br>3/ Up to approximately 7 years after the first participant is randomized<br>4/ Up to approximately 7 years after the first participant is randomized<br>5/ Up to approximately 7 years after the first participant is randomized<br>6/ Up to 30 days after the last dose of study medication
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