A Study of Ibrutinib With Rituximab in Relapsed or Refractory Mantle Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to provide continued access to treatment for participants who continue to benefit from treatment.

Detailed Description
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Mantle cell lymphoma (MCL) is an uncommon and incurable clinicopathologic subtype of B-cell non-Hodgkin Lymphoma (NHL). Ibrutinib is a first-in-class potent, orally administered, covalently-binding small molecule inhibitor of Bruton's tyrosine kinase (BTKi) for the treatment of B-cell malignancies and chronic graft-versus-host disease. The primary hypothesis of the study is to provide continued access to treatment for participants who continue to benefit from treatment. The study will include a screening phase (up to 30 days prior to randomization), a treatment phase (from randomization until study treatment discontinuation). safety assessments include adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, vital signs, electrocardiogram (ECG), physical examination. The Phase 2 exploratory objectives and endpoints of characterization of pharmacokinetic and pharmacodynamic of ibrutinib may continue to be evaluated using blood samples already collected. The total duration of the study will be up to 2 years 1 month.

Official Title
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A Randomized, Controlled, Open-label, Multicenter, Inferentially Seamless Phase 2/3 Study of Ibrutinib in Combination With Rituximab Versus Physician's Choice of Lenalidomide Plus Rituximab or Bortezomib Plus Rituximab in Participants With Relapsed or Refractory Mantle Cell Lymphoma

Conditions
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Lymphoma, Mantle-Cell

Intervention / Treatment
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* Drug: Ibrutinib
* Drug: Lenalidomide
* Drug: Rituximab
* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 1 prior treatment regimen for mantle cell lymphoma (MCL) excluding inhibitor of Bruton's tyrosine kinase (BTKi) Documented disease progression or relapse following the last anti-MCL treatment At least 1 measurable site of disease on cross-sectional imaging that is greater than or equal to (>=) 2.0 centimeters (cm) in the longest diameter and measurable in 2 perpendicular dimensions per computed tomography (CT) Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 Exclusion Criteria: Prior therapy with ibrutinib or other BTK inhibitor Prior treatment with both lenalidomide and bortezomib. Prior treatment with only 1 of these therapies is allowed Major surgery within 4 weeks of randomization Concurrent enrollment in another therapeutic investigational study Known central nervous system lymphoma History of stroke or intracranial hemorrhage within 6 months prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib)<br>Participants will receive rituximab 375 milligrams per meter square (mg/m^2) intravenously (IV) on Day 1 of Cycles 1 to 6 with ibrutinib 560 milligrams (mg) orally, once daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days). | Drug: Ibrutinib<br>* Ibrutinib capsules will be administered orally.<br>* Other names: JNJ-54179060, IMBRUVICA, PCI-32765;Drug: Rituximab<br>* Rituximab will be administered IV.<br>|
| Experimental: Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib)<br>Participants will receive rituximab 375 mg/m^2 IV on Day 1 of Cycles 1 to 6 with ibrutinib 420 mg orally, once daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days). | Drug: Ibrutinib<br>* Ibrutinib capsules will be administered orally.<br>* Other names: JNJ-54179060, IMBRUVICA, PCI-32765;Drug: Rituximab<br>* Rituximab will be administered IV.<br>|
| Experimental: Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib)<br>Participants will receive rituximab 375 mg/m^2 IV on Day 1 of Cycles 1 to 6 with ibrutinib 140 mg orally, twice daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days). | Drug: Ibrutinib<br>* Ibrutinib capsules will be administered orally.<br>* Other names: JNJ-54179060, IMBRUVICA, PCI-32765;Drug: Rituximab<br>* Rituximab will be administered IV.<br>|
| Experimental: Phase 2: Treatment Arm B (Rituximab plus Lenalidomide or Bortezomib)<br>Participants will receive rituximab 375 mg/m^2 IV on Day 1 of Cycles 1 to 6 (each cycle length is 21 or 28 days) with physician's choice of either lenalidomide 20 mg orally, once daily from Day 1 through Day 21 of 28-day cycle or bortezomib 1.3 mg/m^2 IV or subcutaneously (SC) on Days 1, 4, 8 and 11 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Lenalidomide<br>* Lenalidomide capsules will be administered orally.<br>Drug: Rituximab<br>* Rituximab will be administered IV.<br>Drug: Bortezomib<br>* Bortezomib will be administered either intravenously or subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) that Resulted in Discontinuation of Treatment, Severe AE, or Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE defined as results in death, is life-threatening (the participant was at risk of death at the time of the event. It does not refer to an event that hypothetically might have caused death if it were more severe), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a suspected transmission of any infectious agent via a medicinal product, and is Medically Important. | Up to 6 months | 
| Number of Participants with Abnormalities in Clinical Laboratory Parameters | Number of participants with abnormalities in clinical laboratory parameters (hematology and serum chemistry) will be reported. | Up to 6 months |