Clinical trial NCT03039114: Study Evaluating Safety and Efficacy of INCB050465 Combined With Bendamustine and Obinutuzumab in Relapsed or Refractory Follicular Lymphoma (CITADEL-102)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Keywords: Follicular lymphoma
relapsed
refractory
non-Hodgkin lymphoma
phosphatidylinositol 3-kinase (PI3K)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2017-02-01
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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).

Primary outcomes:
measure: 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)
timeFrame: Screening through 30-35 days after end of treatment, up to approximately 34 months per subject
Secondary outcomes:
measure: Objective response rate based on Lugano classification criteria
timeFrame: Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
measure: Complete response rate based on Lugano classification criteria
timeFrame: Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
measure: Duration of response
timeFrame: Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
measure: Progression-free survival
timeFrame: Protocol-defined timepoints throughout the treatment period, up to approximately 34 months per subject
measure: Overall survival
timeFrame: From the date of the first dose of study drug until death due to any cause, assessed up to approximately 34 months per subject
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Health
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Fairway
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders (CCBD) - Bethesda
state: Maryland
city: Lake Success
country: United States
facility: Clinical Research Alliance
state: New York
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin & Affiliated Hospitals
state: Wisconsin
city: Ostrava
country: Czechia
facility: FN Ostrava / Ostrava
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Copenhagen
country: Denmark
facility: The Finsen Centre, National Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Ematologia LA Seragnoli
city: Brescia
country: Italy
facility: A.O. Spedali Civili
city: Brescia
country: Italy
facility: UO Ematologia ASST Spedali Civili
city: Barcelona
country: Spain
facility: Hospital Germans Trias Pujol
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
affiliation: Incyte Corporation
name: Fitzroy Dawkins, MD
role: STUDY_DIRECTOR
References: