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

• Register: EUCTR
• Last refreshed on: 1 February 2022
• Main ID: EUCTR2013-003093-27-BE
• Date of registration: 19/11/2013
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Participants with Previously Treated Indolent Non-Hodgkin Lymphoma
• Scientific title: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination with Either Bendamustine and Rituximab (BR) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects with Previously Treated Indolent Non-Hodgkin Lymphoma (iNHL)
• Date of first enrolment: 10/03/2014
• Target sample size: 400
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003093-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, China, France, Germany, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
- Histologically confirmed diagnosis of B-cell indolent Non-Hodgkin lymphoma with histological subtype limited to follicular lymphoma or marginal zone lymphoma, at initial diagnosis and without evidence of pathological transformation or clinical signs suggesting transformation
- At least 1 prior treatment with a CD20 antibody combination chemo- immunotherapy regimen
- Disease that has relapsed or was refractory after prior chemo-immunotherapy
- 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
- Requires treatment with strong CYP3A inhibitors
- Clinically significant cardiovascular disease
- Known history of human immunodeficiency virus or active hepatitis C
virus (HCV; ribonucleic acid [RNA] polymerase chain reaction [PCR]-
positive) or active hepatitis B virus (HBV; DNA PCR-positive) infection or
any uncontrolled active systemic infection regarding 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Indolent Non-Hodgkin Lymphoma (iNHL)
MedDRA version: 20.0 Level: HLT Classification code 10029621 Term: Non-Hodgkin's lymphomas unspecified histology indolent System Organ Class: 100000004851

Intervention(s)

Product Name: Ibrutinib
Product Code: JNJ-54179060
Pharmaceutical Form: Capsule
INN or Proposed INN: Ibrutinib
Current Sponsor code: Ibrutinib
Other descriptive name: IBRUTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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).

Primary end point(s): Progression-free survival

Secondary Objective: The secondary objectives are to compare treatment groups in terms of the following:
? overall survival (OS)
? complete response rate (CR)
? overall response rate ORR (CR+PR)
? duration of response (DOR)
? patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
? safety of ibrutinib when combined with BR or R-CHOP

Timepoint(s) of evaluation of this end point: Up to approximately 7 years after the first participant is randomized

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1/ Up to approximately 7 years after the first participant is randomized
2/ Up to approximately 7 years after the first participant is randomized
3/ Up to approximately 7 years after the first participant is randomized
4/ Up to approximately 7 years after the first participant is randomized
5/ Up to approximately 7 years after the first participant is randomized
6/ Up to 30 days after the last dose of study medication

Secondary end point(s): Overall survival
1/ Overall survival
2/ Complete response rate
3/ Overall response rate
4/ Duration of response
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)
6/ Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)

Secondary ID(s)

PCI-32765FLR3001

2013-003093-27-SE

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date: 10/03/2014
Contact: