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
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ClinicalTrials.gov Identifier: NCT01776840 |
Recruitment Status :
Active, not recruiting
First Posted : January 28, 2013
Last Update Posted : May 20, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Mantle Cell Lymphoma | Drug: Bendamustine Drug: Rituximab Drug: Ibrutinib Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 523 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official 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 |
Actual Study Start Date : | May 16, 2013 |
Actual Primary Completion Date : | June 30, 2021 |
Estimated Study Completion Date : | December 15, 2025 |
Arm | Intervention/treatment |
---|---|
Placebo Comparator: Treatment Arm A |
Drug: Bendamustine
90 mg/m2 administered intravenously on Days 1-2, Cycles 1-6 Drug: 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 Drug: 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 |
Experimental: Treatment Arm B |
Drug: Bendamustine
90 mg/m2 administered intravenously on Days 1-2, Cycles 1-6 Drug: 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 Drug: 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 |
- Progression-free survival [ Time Frame: 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) ]
- 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) ]
- Overall response rate [ Time Frame: 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) [ 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 ]
- 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) ]
- Duration of response [ Time Frame: Up to the end-of-study visit up to 7 years after the last patient is randomized ]
- Time-to-next treatment [ Time Frame: 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 [ Time Frame: Up to 30 days after the last dose of any study treatment ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 65 Years and older (Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 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
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 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01776840

Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Responsible Party: | Janssen Research & Development, LLC |
ClinicalTrials.gov Identifier: | NCT01776840 |
Other Study ID Numbers: |
CR100967 PCI-32765MCL3002 ( Other Identifier: Janssen Research & Development, LLC ) U1111-1137-0389 ( Other Identifier: Universal Trial Number ) 2012-004056-11 ( EudraCT Number ) |
First Posted: | January 28, 2013 Key Record Dates |
Last Update Posted: | May 20, 2022 |
Last Verified: | May 2022 |
Studies a U.S. FDA-regulated Device Product: | No |
Mantle cell lymphoma Ibrutinib Bruton's tyrosine kinase inhibitor Bendamustine hydrochloride Rituximab |
Lymphoma Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Rituximab |
Bendamustine Hydrochloride Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |