A Study of Parsaclisib, a PI3Kδ Inhibitor, in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma

Study Overview
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Brief Summary
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This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study of parsaclisib plus BR versus placebo plus BR as first-line treatment of participants with newly diagnosed MCL.

Official Title
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A Phase 3, Randomized, Double-Blind Study Comparing Parsaclisib, a PI3Kδ Inhibitor, in Combination With Bendamustine and Rituximab (BR), With Placebo and BR for the Treatment of Newly Diagnosed Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: parsaclisib
* Drug: rituximab
* Drug: bendamustine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants aged 18 years or older. (Japan aged 20 years or older.) Have received no previous systemic anti-lymphoma therapies. Pathologically confirmed MCL by local laboratory. Histologically confirmed CD20 expression (by flow cytometry or immunohistochemistry) of the MCL cells as assessed by pathology. Ineligible for high-dose chemotherapy and autologous stem cell transplantation. Radiographically (CT, MRI) measurable lymphadenopathy per the Lugano criteria for response assessment (Cheson et al 2014). ECOG PS of 0 to 2. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Presence of any lymphoma other than MCL. Presence of CNS lymphoma (either primary or secondary) or leptomeningeal disease. Requires treatment with potent inducers and inhibitors of CYP3A4 Inadequate organ functions including hematopoiesis, liver, and kidney significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, GI, endocrine, pulmonary, neurological, cerebral, or psychiatric disease. History of other malignancy within 2 years of study entry. Known HIV infection, HBV or HCV. HBV or HCV infection: Participants positive for HBsAg or anti-HBc will be eligible if they are negative for HBV-DNA; these participants must receive prophylactic antiviral therapy. Participant's positive for HCV antibody will be eligible if they are negative for HCV-RNA. Clinically significant cardiac disease, congestive heart failure, including unstable angina, acute myocardial infarction, or cardiac conduction issues, within 6 months of randomization. Abnormal ECG findings that are clinically meaningful per investigator's assessment. Women who are pregnant or breastfeeding Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Group A<br>Participants will be administered parsaclisib once daily and will receive Bendamustine and Rituximab periodically for 6 months. | Drug: parsaclisib<br>* parsaclisib will be administered orally once daily.<br>* Other names: INCB050465;Drug: rituximab<br>* rituximab is administered IV on Day 1 of each 28-day cycle for 6 cycles.<br>* Other names: Rituxan;Drug: bendamustine<br>* bendamustine is administered IV on Day 1 and 2 of each 28-day cycle for 6 cycles.<br>* Other names: Treanda;|
| Placebo Comparator: Treatment group B<br>Participants will be administered placebo once daily and will receive Bendamustine and Rituximab periodically for 6 months. | Drug: rituximab<br>* rituximab is administered IV on Day 1 of each 28-day cycle for 6 cycles.<br>* Other names: Rituxan;Drug: bendamustine<br>* bendamustine is administered IV on Day 1 and 2 of each 28-day cycle for 6 cycles.<br>* Other names: Treanda;Drug: Placebo<br>* placebo will be administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Defined as the time from the date of randomization until the date of first-documented disease progression, as determined by an Independent Review Committee (IRC) based on the Lugano criteria, or death from any cause, whichever happens first. | 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time from the date of randomization until death from any cause. | 10 years | 
| Objective Response Rate | Defined as the proportion of participants with a Complete Response (CR) or Partial Response (PR) as determined by an IRC- provided radiographic disease assessment of response according to response criteria for lymphomas. | 7 Years | 
| Complete Response Rate | Defined as the proportion of participants with a CR as determined by an IRC- provided radiographic disease assessment of response according to response criteria for lymphomas. | 7 Years | 
| Duration of Response | Defined as the time from first-documented evidence of CR or PR until first documented disease progression or death from any cause, whichever happens first, among participants who achieve an objective response, as determined by radiographic disease assessment provided by an IRC. | 7 Years | 
| Duration Of Complete Response | Defined as the time from the first evidence of CR to the date of first documented disease progression or death from any cause, whichever happens first, among participants who achieve a CR, as determined by radiographic disease assessment provided by an IRC. | 7 Years | 
| Disease Control Rate | Defined as the proportion of participants who achieved a response of CR, PR, or Stable Disease (SD) assessed by an IRC. | 7 Years | 
| Event Free Survival | Defined as the time from date of randomization to date of first documented progression, as determined by radiographic disease assessment provided by an IRC, administration of a new anti lymphoma treatment, or death from any cause, whichever happens first. | 7 Years | 
| Time To Next anti-Lymphoma Treatment | Defined as the time from date of randomization to date of first documented administration of a new anti-lymphoma treatment. | 7 Years | 
| Progression-Free Survival on next anti-lymphoma treatment | Defined as the time from the date of randomization to the date of first documented disease progression as reported by investigator after next anti-lymphoma treatment or death from any cause, or start of a third anti-lymphoma treatment since randomization, whichever happens first. | 7 Years | 
| Treatment Emergent Adverse Events | Adverse events reported for the first time or worsening of a pre-existing event after the first dose of study drug/treatment. | 7 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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parsaclisib, newly diagnosed, bendamuastine, rituximab, PI3Kδ