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

JRCT ID: jRCT2051230017

Registered date:16/04/2023

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Mantle cell lymphoma
• Date of first enrollment: 30/10/2013
• Target sample size: 523
• Countries of recruitment: Argentina,Japan,Australia,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czechia,Japan,Germany,Japan,Spain,Japan,France,Japan,United Kingdom Of Great Britain,Japan,Greece,Japan,Hungary,Japan,Ireland,Japan,Israel,Japan,Republic Of Korea,Japan,Mexico,Japan,Netherlands,Japan,Poland,Japan,Puerto Rico,Japan,Russian Federation,Japan,Slovakia,Japan,Sweden,Japan,Turkey,Japan,Taiwan,Japan,Ukraine,Japan,United States Of America,Japan
• Study type: Interventional

Intervention(s)

Bendamustine
90 mg/m2 administered intravenously on Days 1-2, Cycles 1-6
Treatment Arm A
Treatment Arm B

Rituximab
375 mg/m2 administered intravenously on Day 1, Cycles 1-6; if complete
response or partial response is achieved, 375 mg/m2 is administered on Day 1 of every second cycle for a maximum of 12 additional doses
Treatment Arm A
Treatment Arm B

Ibrutinib
560 mg (4 x 140 mg capsules) administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end
Treatment Arm B

Placebo
4 capsules administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or the final analysis of progression-free survival
Treatment Arm A

Outcome(s)

Primary Outcome

Progression-free survival
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

- Overall survival
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)

- Overall response rate
Up to the end-of-study visit up to 7 years after the last patient is randomized

- Number of participants with change in Lym subscale scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT Lym)
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

- Minimal residual disease negative rate
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)

- Duration of response
Up to the end-of-study visit up to 7 years after the last patient is randomized

- Time-to-next treatment
Up to the end-of-study visit up to 7 years after the last patient is randomized

- Number of participants affected by an adverse event
Up to 30 days after the last dose of any study treatment

- Oral plasma clearance of ibrutinib as derived from population pharmacokinetics
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

- Oral volume of distribution at steady state of ibrutinib as derived from population pharmacokinetics
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

- Area under the concentration curve of ibrutinib as derived from population pharmacokinetics
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

- Minimum observed plasma concentration of ibrutinib as derived from population pharmacokinetics
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

-Maximum observed plasma concentration of ibrutinib as derived from population pharmacokinetics
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

Key inclusion & exclusion criteria

• Age minimum: >= 65age old
• Age maximum: Not applicable
• Gender: Both

Include 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 other relevant markers (eg, CD19, CD20, 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

Exclude 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 CYP3A 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

Related Information

• Primary Sponsor: Fujikawa Ei
• Secondary ID(s): NCT01776840,2012-004056-11