A Study of Parsaclisib, a PI3Kδ Inhibitor, in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma (CITADEL-310)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Mantle Cell Lymphoma
• Intervention / Treatment: Drug: parsaclisib; Drug: rituximab; Drug: bendamustine; Drug: Placebo

• 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.)
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Anticipated): March 11, 2022
• Primary Completion (Anticipated): August 15, 2030
• Study Completion (Anticipated): July 7, 2034

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: rituximab; newly diagnosed; PI3Kδ; parsaclisib; bendamuastine
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Bendamustine Hydrochloride; Rituximab
• Other Study ID Numbers: INCB 50465-310

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; Statistical Analysis Plan (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