INCB050465 in Combination With Rituximab, Bendamustine and Rituximab, or Ibrutinib in Participants With Previously Treated B-Cell Lymphoma (CITADEL-112)

A Phase 1, Open-Label, Dose-Finding Study of INCB050465 in Combination With Investigator Choice of Rituximab, Bendamustine and Rituximab, or Ibrutinib in Participants With Previously Treated B-Cell Lymphoma (CITADEL-112)

The purpose of this study is to evaluate the safety and tolerability of parsaclisib when combined with rituximab, bendamustine and rituximab, or ibrutinib in participants with relapsed or refractory B-cell lymphoma.

Study Overview

• Status: Completed
• Conditions: B-cell Lymphoma
• Intervention / Treatment: Drug: Parsaclisib; Drug: Rituximab; Drug: Bendamustine; Drug: Ibrutinib

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy, 25123
    • ASST Spedali Civili di Brescia
  • Monza, Italy, 20835
    • Azienda Ospedaliera San Gerardo di Monza
  • Pisa, Italy, 56126
    • Azienda Ospedaliera Universitaria Pisana
  • Ravenna, Italy, 48121
    • Ospedale Delle Croci - Ematologia Ravenna
• Spain
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall d Hebron
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Salamanca, Spain, 37007
    • Hospital Clínico Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitario Y Politecnic La Fe
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center - Out Pt.
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Center of Nevada
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology
    • Dallas, Texas, United States, 75246
      • Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77054
      • Smith Clinic
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women, aged 18 years or older on the day of signing the Informed Consent Form (ICF).
• Histologically confirmed indolent/aggressive DLBCL, FL, MZL, or MCL.
• Participants with DLBCL, MZL or MCL must have received at least 1 prior line of systemic therapy with documented progression or documented failure to achieve CR or PR after the most recent systemic treatment regimen.
• Participants with FL must have received at least 2 prior lines of systemic therapy with documented progression or documented failure to achieve CR or PR after the most recent systemic treatment regimen.
• Ineligible for stem cell transplant.
• Participants with DLBCL must have failed or refused stem cell transplantation or failed first-line salvage therapy if ineligible for transplantation.
• Must be willing to undergo an incisional or excisional lymph node or tissue biopsy or to provide a lymph node or tissue biopsy from the most recent available archival tissue.
• Life expectancy of > 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2 (see Appendix D).
• Willingness to avoid pregnancy or fathering a child.
• Ability to comprehend and willingness to sign an ICF

Exclusion Criteria:

• Evidence of transformed non-Hodgkin lymphoma histologies (with the exception of FL).
• Histologically confirmed rare non-Hodgkin B-cell subtypes.
• History of or central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease.
• Prior treatment with idelalisib, other selective PI3Kδ inhibitors, or a pan-PI3K inhibitor.

• For participants to be treated with bendamustine (Treatment B), prior treatment with bendamustine (within 12 months of the start of study treatment). Participants with prior bendamustine treatment (> 12 months before the start of study treatment) are eligible if they meet the following criteria:

  • Did not discontinue because of tolerability concerns.
  • Achieved either partial response (PR) or complete response (CR) to the bendamustine regimen of at least 12 months in duration before relapse/progression.
  • Experienced progression following a regimen containing an alkylating agent.
• For participants to be treated with ibrutinib (Treatment C), prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor.
• Allogeneic stem cell transplant within the last 6 months or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment.
• Active graft-versus-host disease following allogeneic transplant.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Parsaclisib + Rituximab	Drug: Parsaclisib; Parsaclisib administered orally once daily for 8 weeks followed by once weekly.; Other Names: INCB050465; Drug: Rituximab; Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group.; Other Names: Rituxan
Experimental: Treatment B; Parsaclisib + Bendamustine + Rituximab	Drug: Parsaclisib; Parsaclisib administered orally once daily for 8 weeks followed by once weekly.; Other Names: INCB050465; Drug: Rituximab; Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group.; Other Names: Rituxan; Drug: Bendamustine; Bendamustine administered intravenously on Days 1 and 2 of each cycle for up to 6 cycles.; Other Names: Treanda, Bendeka
Experimental: Treatment C; Parsaclisib + Ibrutinib	Drug: Parsaclisib; Parsaclisib administered orally once daily for 8 weeks followed by once weekly.; Other Names: INCB050465; Drug: Ibrutinib; Ibrutinib administered orally once daily.; Other Names: Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-emergent adverse events (TEAEs)	A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment.	Up to approximately 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apparent clearance of parsaclisibin combination with rituximab, bendamustine and rituximab, or ibrutinib	Measured to assess the plasma pharmacokinetic profile of parsaclisib in combination with rituximab, bendamustine and rituximab, and ibrutinib.	Up to approximately 1 month.
Apparent volume of distribution of parsaclisib in combination with rituximab, bendamustine and rituximab, or ibrutinib	Measured to assess the plasma pharmacokinetic profile of parsaclisib in combination with rituximab, bendamustine and rituximab, and ibrutinib.	Up to approximately 1 month.

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Peter Langmuir, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2018
• Primary Completion (Actual): June 27, 2022
• Study Completion (Actual): June 27, 2022

Study Registration Dates

• First Submitted: January 25, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Diffuse large B-cell lymphoma (DLBCL); follicular lymphoma (FL); marginal zone lymphoma (MZL); mantle cell lymphoma (MCL); phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Bendamustine Hydrochloride; Rituximab; Ibrutinib
• Other Study ID Numbers: INCB 50465-112 (CITADEL-112); Parsaclisib (Other Identifier: Incyte Corporation); 2017-004088-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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