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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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B-cell Lymphoma

Intervention / Treatment
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* Drug: Parsaclisib
* Drug: Rituximab
* Drug: Bendamustine
* Drug: Ibrutinib


Participation Criteria
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Eligibility Criteria
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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.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Parsaclisib + Rituximab | Drug: Parsaclisib<br>* Parsaclisib administered orally once daily for 8 weeks followed by once weekly.<br>* Other names: INCB050465;Drug: Rituximab<br>* Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group.<br>* Other names: Rituxan;|
| Experimental: Treatment B<br>Parsaclisib + Bendamustine + Rituximab | Drug: Parsaclisib<br>* Parsaclisib administered orally once daily for 8 weeks followed by once weekly.<br>* Other names: INCB050465;Drug: Rituximab<br>* Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group.<br>* Other names: Rituxan;Drug: Bendamustine<br>* Bendamustine administered intravenously on Days 1 and 2 of each cycle for up to 6 cycles.<br>* Other names: Treanda, Bendeka;|
| Experimental: Treatment C<br>Parsaclisib + Ibrutinib | Drug: Parsaclisib<br>* Parsaclisib administered orally once daily for 8 weeks followed by once weekly.<br>* Other names: INCB050465;Drug: Ibrutinib<br>* Ibrutinib administered orally once daily.<br>* Other names: Imbruvica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, Diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL)