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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Parsaclisib
* Drug: Hexal
* Drug: Gazyvaro


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parsaclisib + Hexal and Gazyvaro<br> | Drug: Parsaclisib<br>* Parsaclisib at the protocol-defined starting dose administered once daily for 8 weeks followed by once weekly.<br>* Other names: INCB050465;Drug: Hexal<br>* Bendamustine 90 mg/m^2 administered intravenously at protocol-defined timepoints.<br>* Other names: Bendamustine;Drug: Gazyvaro<br>* Obinutuzumab 1000 mg by intravenous infusion at protocol-defined timepoints.<br>* Other names: Obinutuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Follicular lymphoma, relapsed, refractory, non-Hodgkin lymphoma, phosphatidylinositol 3-kinase (PI3K)