A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2013-000959-40-NL
• Date of registration: 27/09/2013
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
• Scientific title: 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
• Date of first enrolment: 06/12/2013
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000959-40
• 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, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, Taiwan, 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:
- 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- defined 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
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 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

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


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

Health Condition(s) or Problem(s) studied

Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
MedDRA version: 20.0 Level: LLT Classification code 10012820 Term: Diffuse large B-cell lymphoma NOS System Organ Class: 100000004864

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

Intervention(s)

Product Name: Ibrutinib
Product Code: JNJ-54179060
Pharmaceutical Form: Capsule
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Current Sponsor code: JNJ-54179060
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 is to evaluate if the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) prolongs event-free survival (EFS) compared with R-CHOP alone in subjects with newly diagnosed non-GCB subtype of DLBCL selected by IHC or in subjects with newly diagnosed ABC subtype of DLBCL identified by GEP or both patient populations.

Timepoint(s) of evaluation of this end point: Up to disease progression, relapse from complete response, initiation of subsequent systemic antilymphoma therapy after completion of at least 6 cycles of R-CHOP therapy, or death, whichever occurs first, up to Year 7

Primary end point(s): Event-free survival

Secondary Objective: The secondary objectives are to:
? Evaluate PFS
Evaluate CR rate
? Evaluate overall survival?
? Evaluate patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
? Characterize the pharmacokinetics of ibrutinib and to explore the potential relationships between ibrutinib metrics of exposure with relevant clinical or biomarker information
? Evaluate the safety of ibrutinib when combined with R-CHOP

The exploratory objectives are to:
? Evaluate patient-reported outcomes (PRO), related to well-being and general health status, utilizing the FACT-Lym and EuroQol questionnaire (EQ-5D-5L)
? Explore the relationship between relevant biomarkers (eg, GEP, gene mutations) with clinical outcomes and mechanism of resistance

Secondary Outcome(s)

Secondary end point(s): - Progression-free survival
-Complete Response
- Overall survival
- Time to worsening symptoms in the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
- Oral plasma clearance of ibrutinib
- Oral volume of distribution at steady state of ibrutinib
- Area under the plasma concentration-time curve of ibrutinib
- Minimum observed plasma concentration of ibrutinib
- Number of participants affected by an adverse event

Timepoint(s) of evaluation of this end point: - Up to disease progression, relapse from complete response, or death, whichever occurs first, up to Year 7
-Up to completion of chemotherapy treatment, up to Year 7
- Up to the date of the participants death, up to Year 7
- Up to the start date of the worsening of patient symptoms, up to Year 7
- Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
- Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
- Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
- Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
- Up to 30 days after the last dose of study medication

Secondary ID(s)

2013-000959-40-SE

PCI-32765DBL3001

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date:
Contact: