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)

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

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) .

Study Overview

• Status: Withdrawn
• Conditions: Marginal Zone Lymphoma (MZL); Follicular Lymphoma ( FL)
• Intervention / Treatment: Drug: parsaclisib; Drug: rituximab; Drug: obinutuzumab

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Anticipated): December 30, 2022
• Primary Completion (Anticipated): December 20, 2028
• Study Completion (Anticipated): August 25, 2032

Study Registration Dates

• First Submitted: March 10, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 18, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: rituximab; Relapsed/Refractory; obinutuzumab; parsaclisib
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab; Obinutuzumab
• Other Study ID Numbers: INCB 50465-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No