To Evaluate Efficacy and Safety of Parsaclisib Plus Either Rituximab or Obinutuzumab in R/R Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL) (CITADEL-302)

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 investigator's choice of either rituximab or obinutuzumab versus placebo plus investigator's choice of rituximab or obinutuzumab for the treatment of participants with R/R FL or MZL. The Participants will be stratified in a 1:1 randomization ratio by investigator's choice of rituximab or obinutuzumab prior to randomization, time since last antilymphoma therapy (≤ 2, > 2 years), and disease histology (MZL or FL) .

Official Title
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A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Parsaclisib Plus Investigator's Choice of Either Rituximab or Obinutuzumab in Participants With Relapsed or Refractory Follicular Lymphoma and Marginal Zone Lymphoma

Conditions
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Follicular Lymphoma ( FL), Marginal Zone Lymphoma (MZL)

Intervention / Treatment
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* Drug: parsaclisib
* Drug: rituximab
* Drug: obinutuzumab


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). Histologically confirmed Grade 1, 2, or 3a FL or nodal MZL, splenic MZL, or extra nodal MZL Prior systemic treatment with at least 1 anti-CD20 mAb (either as monotherapy or in combination as chemoimmunotherapy) Documented disease that has relapsed or progressed or was refractory after the most recent prior systemic therapy. Note: Participants must not be refractory to anti-CD20 mAb Radiographically (CT, MRI) measurable lymphadenopathy per the Lugano criteria for response assessment (Cheson et al 2014). ECOG PS of 0 to 2 Adequate organ functions including hematopoiesis, liver, and kidney Willingness to avoid pregnancy or fathering children Exclusion Criteria: Women who are pregnant or breastfeeding. Known histological transformation from indolent NHL to an aggressive NHL (eg, diffuse large B-cell lymphoma). Presence of CNS lymphoma (either primary or secondary) or leptomeningeal disease. Prior treatment with PI3K inhibitors. Inadequate washout of immunosuppressive therapy, anticancer medications and investigational drugs. Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, GI, endocrine, pulmonary, neurological, cerebral, cardiac, infectious, or psychiatric disease. Known HIV infection. 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. Participants positive for HCV antibody will be eligible if they are negative for HCV-RNA. History of other malignancy within 2 years of study entry. Any condition that would, in the investigator's judgment, interfere with full participation in the study.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group A<br>Participants will be administered with parsaclisib in combination with investigator choice of rituximab or obinutuzumab. | Drug: parsaclisib<br>* parsaclisib will be administered once daily at 20 mg for 8 weeks followed by 2.5 mg once daily.<br>* Other names: INCB050465;Drug: rituximab<br>* rituximab will be administered intravenously on select days as per protocol.<br>Drug: obinutuzumab<br>* obinutuzumab will be administered intravenously on select days as per protocol.<br>|
| Placebo Comparator: Treatment Group B<br>Participants will be administered with placebo in combination with investigator choice of rituximab or obinutuzumab | Drug: rituximab<br>* rituximab will be administered intravenously on select days as per protocol.<br>Drug: obinutuzumab<br>* obinutuzumab will be administered intravenously on select days as per protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) in R/R FL and MZL participants | Defined as the time from the date of randomization until the first documented disease progression as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014) or death from any cause, whichever occurs first. | 62 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) in R/R FL participants | Defined as the time from the date of randomization until the first documented disease progression as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014) or death from any cause, whichever occurs first. | 62 months | 
| Overall Response Rate (ORR) | Defined as the proportion of participants with a CR or PR as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014). | 62 months | 
| Overall Survival (OS) | Defined as the time from the date of randomization until death from any cause. | 10 years | 
| Progression Free Survival (PFS) in R/R MZL participants | Defined as the time from the date of randomization until the first documented disease progression as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014) or death from any cause, whichever occurs first. | 62 months | 
| Complete Response Rate (CRR) | Defined as the proportion of participants with a CR as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014). | 62 months | 
| Duration of Response (DOR) | Defined as the time from the date of first documented evidence of CR or PR until the first documented disease progression or death from any cause, whichever occurs first, among participants who achieve an objective response as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014). | 62 months | 
| Disease Control Rate (DCR) | Defined as the proportion of participants who achieve best overall response of CR, PR, or SD (Cheson et al 2014) as determined by IRC. | 62 months | 
| Event Free Survival (EFS) | Defined as the time from the date of randomization to the first documented disease progression as determined by radiographic disease assessment provided by IRC, the initiation of a new antilymphoma therapy, or death from any cause, whichever occurs first. | 62 months | 
| Time To Next antiLymphoma Therapy (TTNLT) | Defined as the time from the date of randomization to the first documented administration of a new antilymphoma therapy. | 62 months | 
| Progression-Free Survival on next antilymphoma therapy (PFS2) | Defined as the time from the date of randomization to the first documented disease progression as reported by the investigator after the initiation of a new antilymphoma therapy, death from any cause, or start of a third antilymphoma therapy since randomization in the study, whichever occurs first. | 62 months | 
| Number of Treatment Emergent Adverse Events (TEAE's) | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. | 62 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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parsaclisib, Relapsed/Refractory, obinutuzumab, rituximab