Study of Safety and Efficacy of BCL201 and Idelalisib in Patients With FL and MCL

Study Overview
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Brief Summary
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This is a phase Ib multi-center, open-label study: escalation part followed by expansion part. The primary purpose of the Phase Ib CBCL201X2102C study is to characterize the safety and tolerability of BCL201 combined with idelalisib in patients with FL and MCL. Approximately 65 patients are to be enrolled. The primary endpoint for the Phase Ib is frequency, severity and seriousness of AEs, lab abnormalities and other safety parameters such as ECG changes. An adaptive Bayesian logistic regression model (BLRM) will guide the dose escalation to determine the MTD/RDE in phase Ib. In addition Bayesian regression models will be used to estimate the dose-exposure relationships for both BCL201 and idelalisib in order to guide the escalation steps. A Bayesian method for the expansion part will be used for the primary activity objective. The study data will be analyzed and reported based on all patients' data of the escalation and expansion part.

Official Title
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A Phase Ib Dose Escalation Study of BCL201 in Combination With Idelalisib in Patients With Follicular Lymphoma (FL) and Mantle Cell Lymphoma (MCL)

Conditions
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Follicular Lymphoma, Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: BCL201
* Drug: Idelalisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of FL or MCL according to WHO 2008 Relapsed or refractory with at least one (FL) or two (MCL), but not more than four, prior lines of antineoplastic regimens. Either FDG-avid on FDG-PET or measurable disease by CT on cross sectional imaging: > 1.5 cm for nodal lesion, > 1.0 cm for extra nodal lesion. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Exclusion Criteria: For dose escalation part: Patients with MCL at high risk for tumor lysis syndrome Prior treatment with PI3Kδ or Bcl-2 inhibitors. Any other malignant disease History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis Inadequate organ function Concomitant treatment with: Strong CYP3A4/5 inducers or inhibitors Sensitive CYP3A4/5 substrates or CYP3A4/5 substrates with narrow therapeutic index (NTI) Sensitive CYP2D6 substrates or CYP2D6 substrates with NTI Selected dual substrates of CYP3A4/5 and CYP2C8 Selected dual substrates of CYP3A4/5 and CYP2D6 Selected dual substrates of OATP and CYP450 Selected dual substrates of CYP3A4/5 and P-gp NTI P-gp substrates QT prolonging drugs with a known risk to induce TdP Proton pump inhibitors Treatment by warfarin or equivalent vitamin K antagonists. Other investigational therapies Herbal preparations/ medications Grapefruit, Seville oranges or products containing either juice Other protocol-defined inclusion/exclusion may apply.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Follicular lymphoma (FL)<br> | Drug: BCL201<br> <br> * Other names: S55746;Drug: Idelalisib<br> <br> * Other names: Idela;|
| Experimental: Mantle cell lymphoma (MCL)<br> | Drug: BCL201<br> <br> * Other names: S55746;Drug: Idelalisib<br> <br> * Other names: Idela;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | Characterized by Frequency, severity and seriousness of AEs, lab abnormalities and other safety parameters such as electrocardiogram (ECG) changes | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of dose limiting toxicities (DLTs) |  | 24 months | 
| Exposure to BCL201 and idelalisib as measured by AUC0-24h at C1D15 |  | Cycle = 28 days | 
| Plasma concentration of BCL201, idelalisib and GS-563117 (metabolite of idelalisib) |  | 24 Months | 
| AUC pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 |  | 24 months | 
| Objective Response Rate (ORR) |  | 24 months | 
| Best Overall Response (BOR) |  | 24 months | 
| Duration of Response (DOR) |  | 24 months | 
| Complete Response (CR) |  | 24 months | 
| Partial Response (PR) |  | 24 months | 
| Stable disease (SD) |  | 24 months | 
| Cmax pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FL, BCL201, idelalisib, Follicular lymphoma, mantle cell lymphoma, MCL