Study Evaluating Safety and Efficacy of INCB050465 Combined With Bendamustine and Obinutuzumab in Relapsed or Refractory Follicular Lymphoma (CITADEL-102)

An Open-Label, Dose-Finding, and Cohort-Expansion Phase 1 Study Evaluating Safety and Efficacy of INCB050465 in Combination With Bendamustine and Obinutuzumab in Subjects With Relapsed or Refractory Follicular Lymphoma (CITADEL-102)

The purpose of this study is to evaluate the safety and efficacy of parsaclisib when combined with bendamustine and obinutuzumab in subjects with relapsed or refractory follicular lymphoma (FL).

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Parsaclisib; Drug: Hexal; Drug: Gazyvaro

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Ostrava, Czechia, 70852
    • FN Ostrava / Ostrava
• Denmark
  • Aarhus, Denmark, Dk-8000
    • Aarhus University Hospital
  • Copenhagen, Denmark, DK-2100
    • Rigshospitalet
  • Copenhagen, Denmark, DK-2100
    • The Finsen Centre, National Hospital
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
• Italy
  • Aviano, Italy, 33081
    • Centro di Riferimento Oncologico
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Bologna
  • Bologna, Italy, 40138
    • Policlinico S. Orsola-Ematologia LA Seragnoli
  • Brescia, Italy, 25123
    • A.O. Spedali Civili
  • Brescia, Italy, 25123
    • UO Ematologia ASST Spedali Civili
• Spain
  • Barcelona, Spain, 08916
    • Hospital Germans Trias Pujol
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Hospital Universitario Gregorio Marañón
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocío
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner Health
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders (CCBD) - Bethesda
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert & Medical College of Wisconsin & Affiliated Hospitals

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:

• Histologically confirmed FL.
• Documented CD20+ FL.
• Relapsed or refractory to any prior rituximab-containing regimen.
• Previously treated with a maximum of 4 cancer-directed treatment regimens.
• At least 1 measurable lesion > 1.5 cm in at least 1 dimension by computed tomography or magnetic resonance imaging.
• Must be willing to undergo an incisional or excisional lymph node biopsy of accessible adenopathy or provide the most recent, available archived tumor biopsy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Exclusion Criteria:

• Clinical evidence of transformation to a more aggressive subtype of lymphoma or Grade 3B FL.
• History of central nervous system lymphoma (either primary or metastatic).
• Allogeneic stem cell transplant within the last 6 months, or active graft-versus-host disease following allogeneic transplant or autologous stem cell transplant within the last 3 months before the date of the first dose of study drug administration.
• Use of any potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug.
• Prior treatment with a selective PI3Kδ inhibitor or a pan PI3K inhibitor.

• Prior treatment with bendamustine (within 12 months of the start of study treatment). Subjects 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 or CR to the bendamustine regimen of at least 12 months in duration before relapse/progression.
  • Experienced progression following a regimen containing an alkylating agent.
• Received prior obinutuzumab.
• Received rituximab within 4 weeks of study start.
• Prior treatment-related toxicities that have not resolved to ≤ Grade 1 before the date of study drug administration except for stable chronic toxicities (≤ Grade 2) not expected to resolve (eg, stable Grade 2 peripheral neurotoxicity).
• Received any prior monoclonal antibody (except an anti-CD20 antibody) within 90 days before the date of study start.
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (eg, subjects in whom re-administration with rituximab would be contraindicated for safety reasons).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Parsaclisib + Hexal and Gazyvaro

Drug: Parsaclisib; Parsaclisib at the protocol-defined starting dose administered once daily for 8 weeks followed by once weekly.; Other Names: INCB050465; Drug: Hexal; Bendamustine 90 mg/m^2 administered intravenously at protocol-defined timepoints.; Other Names: Bendamustine; Drug: Gazyvaro; Obinutuzumab 1000 mg by intravenous infusion at protocol-defined timepoints.; Other Names: Gazyva®; Obinutuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of parsaclisib in combination with bendamustine and obinutuzumab in relapsed or refractory FL, assessed by number of subjects with adverse events (AEs)	Screening through 30-35 days after end of treatment, up to approximately 34 months per subject

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate based on Lugano classification criteria	Defined as percentage of subjects with a complete response (CR) and partial response (PR), as determined by investigator assessment of response	Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
Complete response rate based on Lugano classification criteria	Defined as percentage of subjects who achieve a best overall response of CR	Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
Duration of response	Defined as time from first documented evidence of CR or PR until earliest date of disease progression or death due to any cause.	Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
Progression-free survival	Defined as time from the date of the first dose of study drug until the earliest date of disease progression (determined by radiographic disease assessment/Lugano classification criteria) or death due to any cause.	Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
Overall survival	Defined as the time from the date of the first dose of study drug until death due to any cause.	From the date of the first dose of study drug until death due to any cause, assessed up to approximately 34 months per subject

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Fitzroy Dawkins, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Actual): March 30, 2021
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: January 31, 2017
• First Submitted That Met QC Criteria: January 31, 2017
• First Posted (Estimate): February 1, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: non-Hodgkin lymphoma; relapsed; refractory; Follicular lymphoma; phosphatidylinositol 3-kinase (PI3K)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Bendamustine Hydrochloride; Obinutuzumab
• Other Study ID Numbers: INCB 50465-102 (CITADEL-102); Parsaclisib (Other Identifier: Incyte Corporation)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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