Clinical trial NCT03424122: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Lymphoma
Keywords: Diffuse large B-cell lymphoma (DLBCL)
follicular lymphoma (FL)
marginal zone lymphoma (MZL)
mantle cell lymphoma (MCL)
phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-02-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of treatment-emergent adverse events (TEAEs)
timeFrame: Up to approximately 12 months.
Secondary outcomes:
measure: Apparent clearance of parsaclisibin combination with rituximab, bendamustine and rituximab, or ibrutinib
timeFrame: Up to approximately 1 month.
measure: Apparent volume of distribution of parsaclisib in combination with rituximab, bendamustine and rituximab, or ibrutinib
timeFrame: Up to approximately 1 month.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center - Out Pt.
state: Arizona
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Smith Clinic
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio
state: Texas
city: Brescia
country: Italy
facility: Asst Spedali Civili Di Brescia
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo Di Monza
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Ravenna
country: Italy
facility: Ospedale Delle Croci - Ematologia Ravenna
city: Badalona
country: Spain
facility: Hospital Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall D Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario Hm Sanchinarro
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario Y Politecnic La Fe
Study officials:
affiliation: Incyte Corporation
name: Peter Langmuir, MD
role: STUDY_DIRECTOR
References: