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

B-cell Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03424122
• Other study ID #: INCB 50465-112 (CITADEL-112)
• Secondary ID: Parsaclisib
• Status: Completed
• Phase: Phase 1
• Start date: July 2, 2018
• Est. completion date: June 27, 2022

Study information

• Verified date: June 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 27, 2022
• Est. primary completion date: June 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 PI3Kd 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.

Related Conditions & MeSH terms

• B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

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

Locations

Country	Name	City	State
Italy	Asst Spedali Civili Di Brescia	Brescia
Italy	Azienda Ospedaliera San Gerardo Di Monza	Monza
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Ospedale Delle Croci - Ematologia Ravenna	Ravenna
Spain	Hospital Germans Trias I Pujol	Badalona
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital General Universitari Vall D Hebron	Barcelona
Spain	Fundacion Jimenez Diaz University Hospital	Madrid
Spain	Hospital Universitario Hm Sanchinarro	Madrid
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitario Y Politecnic La Fe	Valencia
United States	Texas Oncology	Austin	Texas
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Smith Clinic	Houston	Texas
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	Comprehensive Cancer Center of Nevada	Las Vegas	Nevada
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Texas Oncology San Antonio	San Antonio	Texas
United States	University of Arizona Cancer Center - Out Pt.	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.