Study of Ibrutinib and Rituximab in Treatment Naïve Follicular Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether the addition of ibrutinib will result in prolongation of progression-free survival (PFS) when compared with rituximab alone in treatment naïve participants with follicular lymphoma.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Rituximab Versus Placebo in Combination With Rituximab in Treatment Naïve Subjects With Follicular Lymphoma (PERSPECTIVE)

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: ibrutinib
* Drug: placebo to match ibrutinib
* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of follicular lymphoma CD20+ (Grade 1, 2 or 3a) Ann Arbor Stage II, III or IV disease. Measurable disease Subjects 70 years of age or older; OR subjects 60-69 years of age who have one or more comorbidities. Meets one or more Groupe d'Etude des Lymphomes Folliculaire (GELF) criteria. Adequate hematologic function within protocol-defined parameters. Adequate hepatic and renal function within protocol-defined parameters. ECOG performance status score of 0-2. Exclusion Criteria: Transformed lymphoma Prior treatment for follicular lymphoma. Central nervous system lymphoma or leptomeningeal disease. Currently active, clinically significant cardiovascular disease.

Ages Eligible for Study
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Minimum Age: 60 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (Arm A) ibrutinib + rituximab<br>Participants will receive 560mg of ibrutinib and rituximab 375mg/m^2 weekly x4 with maintenance. | Drug: ibrutinib<br>* ibrutinib 560mg administered orally<br>* Other names: Imbruvica;Drug: rituximab<br>* rituximab 375mg/m^2 IV<br>|
| Placebo Comparator: (Arm B) placebo + rituximab<br>Participants will receive placebo and rituximab 375mg/m^2 weekly x4 with maintenance. | Drug: placebo to match ibrutinib<br>* placebo capsules to match ibrutinib administered orally<br>Drug: rituximab<br>* rituximab 375mg/m^2 IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Progression-Free Survival (PFS) | PFS, is assessed by the investigator, will be analyzed in the intent to treat (ITT) population, comparing the 2 treatment arms (Arm A and Arm B). | 2-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR of the two treatment arms will be compared using the Cochran-Mantel-Haenszel (CMH) chi-square test, stratified by the randomization stratification factors, under the hierarchical procedure. | 2-5 years | 
| Overall Survival | Overall survival is defined as the interval between the date of randomization and the date of the participant's death from any cause. | 2-5 years | 
| Infusion-Related Reaction Rate | Infusion-related reaction rate Arm A vs. Arm B. | 2-5 years | 
| Duration of Response (DOR) as Assessed by Investigator | DOR is defined as the time from the date of the participant's documented disease progression or death due to the disease, whichever occurs first. | 2-5 years | 
| Number of Participants with Adverse Events (AE) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | 2-5 years |