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

• ClinicalTrials.gov Identifier: NCT03424122
• Recruitment Status: Completed
• First Posted: February 6, 2018
• Last Update Posted: June 29, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: January 25, 2018
• First Posted Date: February 6, 2018
• Last Update Posted Date: June 29, 2022
• Actual Study Start Date: July 2, 2018
• Actual Primary Completion Date: June 27, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2018)

Number of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to approximately 12 months. ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 19, 2019)

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

Original Secondary Outcome Measures (submitted: January 31, 2018)

• Apparent clearance of INCB050465 in combination with rituximab, bendamustine and rituximab, or ibrutinib [ Time Frame: Up to approximately 1 month. ]
  Measured to assess the plasma pharmacokinetic profile of INCB050465 in combination with rituximab, bendamustine and rituximab, and ibrutinib.
• Apparent volume of distribution of INCB050465 in combination with rituximab, bendamustine and rituximab, or ibrutinib [ Time Frame: Up to approximately 1 month. ]
  Measured to assess the plasma pharmacokinetic profile of INCB050465 in combination with rituximab, bendamustine and rituximab, and ibrutinib.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: INCB050465 in Combination With Rituximab, Bendamustine and Rituximab, or Ibrutinib in Participants With Previously Treated B-Cell Lymphoma (CITADEL-112)
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-cell Lymphoma

Intervention

• Drug: Parsaclisib
  Parsaclisib administered orally once daily for 8 weeks followed by once weekly.
  Other Name: INCB050465
• Drug: Rituximab
  Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group.
  Other Name: Rituxan
• Drug: Bendamustine
  Bendamustine administered intravenously on Days 1 and 2 of each cycle for up to 6 cycles.
  Other Name: Treanda, Bendeka
• Drug: Ibrutinib
  Ibrutinib administered orally once daily.
  Other Name: Imbruvica

Study Arms

• Experimental: Treatment A
  Parsaclisib + Rituximab
  Interventions:

  • Drug: Parsaclisib
  • Drug: Rituximab
• Experimental: Treatment B
  Parsaclisib + Bendamustine + Rituximab
  Interventions:

  • Drug: Parsaclisib
  • Drug: Rituximab
  • Drug: Bendamustine
• Experimental: Treatment C
  Parsaclisib + Ibrutinib
  Interventions:

  • Drug: Parsaclisib
  • Drug: Ibrutinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 21, 2020): 50
• Original Estimated Enrollment (submitted: January 31, 2018): 81
• Actual Study Completion Date: June 27, 2022
• Actual Primary Completion Date: June 27, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, Spain, United States

Administrative Information

• NCT Number: NCT03424122
• Other Study ID Numbers: INCB 50465-112 (CITADEL-112); Parsaclisib ( Other Identifier: Incyte Corporation )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Peter Langmuir, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: June 2022