A Study of CG-806 in Patients With Relapsed or Refractory CLL/SLL or Non-Hodgkin's Lymphomas

Study Overview
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Brief Summary
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This study is being done to evaluate the safety, tolerability and effectiveness of Oral CG-806 for the treatment of patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or Non-Hodgkin's Lymphomas who have failed or are intolerant to two or more lines of established therapy or for whom no other treatment options are available.

Detailed Description
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This is a multicenter, open-label, Phase Ia/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory CLL/SLL or Non-Hodgkin's Lymphoma patients. This is to be followed by a cohort expansion phase at the MTD or recommended oral dose.

Official Title
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A Phase Ia/b Trial to Evaluate the Safety and Tolerability of CG-806 in Patients With CLL/SLL or Non-Hodgkin's Lymphomas

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: CG-806


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Life expectancy of at least 2 months ECOG Performance Status ≤ 2 Patients must be able to swallow capsules Adequate hematologic parameters, unless cytopenias are disease caused Adequate renal, liver and cardiac function parameters Exclusion Criteria: Patients with GVHD requiring systemic immunosuppressive therapy Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinical significant disease related metabolic disorder Clinically significant intravascular coagulation Treatment with other investigational drugs within 14 days prior to first study treatment administration

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation and Expansion<br>CG-806 will be given orally in ascending doses in patients with relapsed or refractory CLL/SLL or Non-Hodgkin's Lymphomas (escalation cohort), until the maximum tolerated dose or recommended dose is reached. Followed by up to 100 patients enrolled in the expansion cohort at the recommended dose. | Drug: CG-806<br>* CG-806 will be given orally in ascending doses starting at 150 mg PO BID until the maximum tolerated dose or recommended dose is reached.<br>* Other names: Luxeptinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events of CG-806 | To determine the safety and tolerability of CG-806. | Cycle 1 (28 days) | 
| Establish a CG-806 dose that maintains a biologically active plasma concentration | To determine the dose of CG-806 given orally every 12 hours that maintains a biologically active plasma concentration over a period of 28 days. | Cycle 1 (28 days) | 
| Establish recommended dose for future development of CG-806 | To establish the recommended Phase 2 dose (RP2D) of CG-806 for future clinical trials in patients with advanced CLL/SLL or NHL. | Up to 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variables including maximum plasma concentration (Cmax) | Pharmacokinetic variables including maximum plasma concentration (Cmax) | Cycle 1 (28 days) | 
| Pharmacokinetic variables including minimum plasma concentration (Cmin) | Pharmacokinetic variables including minimum plasma concentration (Cmin) | Cycle 1 (28 days) | 
| Pharmacokinetic variables including Area Under the Curve (AUC) Pharmacokinetic variables including Area Under the Curve (AUC Pharmacokinetic variables including Area Under the Curve (AUC | Pharmacokinetic variables including Area Under the Curve (AUC) | Cycle 1 (28 days) | 
| Pharmacokinetic variables including volume of distribution | Pharmacokinetic variables including volume of distribution | Cycle 1 (28 days) | 
| Pharmacokinetic variables including clearance | Pharmacokinetic variables including clearance | Cycle 1 (28 days) | 
| Pharmacokinetic variables including serum half-life | Pharmacokinetic variables including serum half-life | Cycle 1 (28 days) | 
| To assess the antitumor activity of CG-806 using FDG PET-CT imaging evaluations | To assess the antitumor activity of CG-806 using FDG PET-CT imaging evaluations | Average 2 Cycles (8 weeks) | 
| Pharmacodynamic biomarkers of drug effect including BTK activity | Pharmacodynamic biomarkers of drug effect including BTK activity | Average 2 cycles (8 weeks) | 
| Pharmacodynamic biomarkers of drug effect including selected mRNA levels | Pharmacodynamic biomarkers of drug effect including selected mRNA levels | Average 2 cycles (8 weeks) | 
| To assess the relative BA of formulation G1 against formulation G2 | To assess the relative bioavailability of original formulation (G1) against new generation formulation (G2). | Cycle 1 (28 days) | 
| To assess the relative BA of formulation G1 against formulation G3 | To assess the relative bioavailability of original formulation (G1) against new generation formulation (G3). | Cycle 1 Lead-Up (3 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FL, Oral, DLBCL, PMBCL, BCLU, GZL, MCL, MZL, WM, LPL, CLL, SLL