A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination with Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma

• Register: EUCTR
• Last refreshed on: 16 September 2013
• Main ID: EUCTR2012-004056-11-IT
• Date of registration: 19/02/2013
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination with Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle 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 Bendamustine and Rituximab (BR) in Subjects With Newly Diagnosed Mantle Cell Lymphoma
• Date of first enrolment: 08/04/2013
• Target sample size: 520
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004056-11
• 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

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Portugal, Russian Federation, Singapore, Slovakia, Spain, Sweden, Taiwan, Thailand, 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:
- Diagnosis of mantle cell lymphoma (MCL) reviewed and approved by central laboratory: diagnosis must include morphology and expression of either cyclin D1 in association with one B-cell marker (eg, CD19, CD20, or PAX5) and CD5 or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
- Clinical Stage II, III, or IV by Ann Arbor Classification
- At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
- No prior therapies for MCL
- Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
- Hematology and biochemical laboratory values within protocol-defined limits
- Agrees to protocol-defined use of effective contraception
- Negative blood 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) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 520

Exclusion criteria:
- Major surgery within 4 weeks of random assignment
- Known central nervous system lymphoma
- Diagnosed or treated for malignancy other than MCL, 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 cervical carcinoma in situ without evidence of disease
- Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
- 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 CYP3A4/5 inhibitors
- 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
- Vaccinated with live, attenuated vaccines within 4 weeks of random assignment
- Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection 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 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

Mantle Cell Lymphoma
MedDRA version: 14.1 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851

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 of this study is to evaluate whether the addition of ibrutinib to bendamustine and rituximab will result in prolongation of PFS in subjects with newly diagnosed MCL who are 65 years of age or older.

Primary end point(s): Progression-free survival

Secondary Objective: The secondary objectives are:
? To evaluate overall survival
? To evaluate the CR rate and overall response rate (CR+PR)
? To evaluate patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
? To evaluate the minimal residual disease (MRD) negative rate
? To evaluate duration of response
? To evaluate time-to-next treatment (TTNT)
? To evaluate the safety of ibrutinib when combined with BR
? To characterize the pharmacokinetics of ibrutinib and explore the potential relationships between ibrutinib metrics of exposure with relevant clinical, pharmacodynamic, or biomarker information

Timepoint(s) of evaluation of this end point: Up to the end-of-study visit until 265 progression-free survival events have been observed (up to 7 years after the last patient is randomized)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See above

Secondary end point(s): 1) Overall survival
Time frame = up to the end-of-study visit until 60% of all enrolled
patients have died (up to 7 years after the last patient is randomized)

2) Overall response rate
Time frame = up to the end-of-study visit up to 7 years after the last
patient is randomized

3) Number of participants with change in Lym subscale scores of the
Functional Assessment of Cancer Therapy-Lymphoma (FACT Lym)
Time frame = screening, Day 1 of the first 6 cycles, then every 12 weeks
in the first 12 months, thereafter every 16 weeks up to 7 years after the
last patient is randomized

4) Minimal residual disease negative rate
Time frame = for participants with complete response, every 12 weeks in
the first 12 months, thereafter every 16 weeks and at disease
progression or up to the end-of-study visit (up to 7 years after the last
patient is randomized)

5) Duration of response
Time frame = up to the end-of-study visit up to 7 years after the last
patient is randomized

6) Time-to-next treatment
Time frame = up to the end-of-study visit up to 7 years after the last
patient is randomized

7) Number of participants affected by an adverse event
Time frame = up to 30 days after the last dose of study medication

8) Oral plasma clearance of ibrutinib as derived from population
pharmacokinetics
Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1
and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose

9) Oral volume of distribution at steady state of ibrutinib as derived from
population pharmacokinetics
Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1
and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose

10) Area under the concentration curve of ibrutinib as derived from
population pharmacokinetics
Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1
and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose

11) Minimum observed plasma concentration of ibrutinib as derived from
population pharmacokinetics
Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1
and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose

12) Maximum observed plasma concentration of ibrutinib as derived
from population pharmacokinetics
Time frame = predose on Day 2 Cycles 1-3, postdose on Day 2 Cycles 1
and 2 at 1, 2, and 4 hours after administration of ibrutinib study dose

Secondary ID(s)

PCI-32765MCL3002

2012-004056-11-SE

Source(s) of Monetary Support

JANSSEN-CILAG SPA