Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution

Study Overview
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Brief Summary
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The use of venetoclax-based therapies for pediatric patients with relapsed or refractory malignancies is increasingly common outside of the clinical trial setting. For patients who cannot swallow tablets, it is common to crush the tablets and dissolve them in liquid to create a solution. However, no PK data exists in adults or children using crushed tablets dissolved in liquid in this manner, and as a result, the venetoclax exposure with this solution is unknown. Primary Objectives • To determine the pharmacokinetics of venetoclax when commercially available tablets are crushed and dissolved into a solution Secondary Objectives To determine the pharmacokinetics of venetoclax solution in patients receiving concomitant strong and moderate CYP3A inhibitors To determine potential pharmacokinetic differences based on route of venetoclax solution administration (ie. PO vs NG tube vs G-tube) To determine the concentration of venetoclax in cerebral spinal fluid when administered as an oral solution

Detailed Description
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Peripheral blood will be drawn at multiple time points to evaluate venetoclax pharmacokinetics in patients who are receiving venetoclax solution made from crushed tablets as part of their oncology treatment.

Official Title
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A Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution in Children and Young Adults With Hematologic Malignancies

Conditions
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AML, ALL, Chronic Myelogenous Leukemia, CML, Myeloproliferative Neoplasm, Non Hodgkin Lymphoma, Hodgkin Lymphoma, Hematologic Malignancy, Leukemia, Lymphoma, Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Burkitt Lymphoma, T-cell Lymphoma, B Cell Lymphoma, Peripheral T Cell Lymphoma, Cutaneous B-Cell Lymphoma

Intervention / Treatment
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* Other: 1. Drug: The Venetoclax PK study is collecting bodily fluid samples (ie., whole blood and optional cerebrospinal fluid) of patients prescribed venetoclax as crushed tablets per standard of care.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: Patients must be <39 years of age at time of study enrollment Diagnosis: Patients may have a diagnosis of any hematologic malignancy Central access: Patients must have a central line for PK blood draws Weight requirement: Patients must weigh at least 5.5 kg at the time of enrollment Venetoclax: Patients must be receiving any dose of venetoclax given as a solution made from crushed tablets by mouth (PO) or via nasogastric (NG), or G-tube as prescribed by their treating oncologist. Concurrent chemotherapy medications: Patients may receive venetoclax as a single agent or in combination with any other chemotherapeutic agents. Exclusion Criteria: Pregnant women are excluded from this study because venetoclax has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on study treatment and for six months following completion.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 38 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children and Young Adults<br>Children and Young Adults who are prescribed venetoclax made from crushed tablets as part of their clinical care. | Other: 1. Drug: The Venetoclax PK study is collecting bodily fluid samples (ie., whole blood and optional cerebrospinal fluid) of patients prescribed venetoclax as crushed tablets per standard of care.<br>* Participants will receive Venetoclax as prescribed by their treating provider as part of their clinical care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) | PK parameters of venetoclax will be described in peripheral blood including: the observed peak plasma concentration (Cmax) | Peripheral blood will be collected on Day 5 and Day 8 of the final venetoclax dose: within 1 hour prior to the administration of venetoclax, then 2 hours, 5 hours, 12 hours, 18 hours, and 24 hours after the administration of venetoclax. | 
| Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) | PK parameters of venetoclax will be described in peripheral blood including: the time to peak (Tmax) | Peripheral blood will be collected on Day 5 and Day 8 of the final venetoclax dose: within 1 hour prior to the administration of venetoclax, then 2 hours, 5 hours, 12 hours, 18 hours, and 24 hours after the administration of venetoclax. | 
| Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) | PK parameters of venetoclax will be described in peripheral blood including: the apparent terminal phase elimination rate constant (β) | Peripheral blood will be collected on Day 5 and Day 8 of the final venetoclax dose: within 1 hour prior to the administration of venetoclax, then 2 hours, 5 hours, 12 hours, 18 hours, and 24 hours after the administration of venetoclax. | 
| Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) | PK parameters of venetoclax will be described in peripheral blood including: the terminal-phase elimination half-life (T1/2) | Peripheral blood will be collected on Day 5 and Day 8 of the final venetoclax dose: within 1 hour prior to the administration of venetoclax, then 2 hours, 5 hours, 12 hours, 18 hours, and 24 hours after the administration of venetoclax. | 
| Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) | PK parameters of venetoclax will be described in peripheral blood including: the areas under plasma concentration curve (AUC) over a 24-hour dose interval (AUC0-24) or for infinite time (AUC0-∞) | Peripheral blood will be collected on Day 5 and Day 8 of the final venetoclax dose: within 1 hour prior to the administration of venetoclax, then 2 hours, 5 hours, 12 hours, 18 hours, and 24 hours after the administration of venetoclax. | 
| Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) | PK parameters of venetoclax will be described in peripheral blood including: oral clearance (CL/F) of venetoclax | Peripheral blood will be collected on Day 5 and Day 8 of the final venetoclax dose: within 1 hour prior to the administration of venetoclax, then 2 hours, 5 hours, 12 hours, 18 hours, and 24 hours after the administration of venetoclax. | 
| Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) | PK parameters of venetoclax will be described in cerebral spinal fluid including: the observed peak plasma concentration (Cmax) | Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points. | 
| Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) | PK parameters of venetoclax will be described in cerebral spinal fluid including: the time to peak (Tmax) | Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points. | 
| Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) | PK parameters of venetoclax will be described in cerebral spinal fluid including: the apparent terminal phase elimination rate constant (β) | Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points. | 
| Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) | PK parameters of venetoclax will be described in cerebral spinal fluid including: the terminal-phase elimination half-life (T1/2) | Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points. | 
| Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) | PK parameters of venetoclax will be described in cerebral spinal fluid including: the areas under plasma concentration curve (AUC) over a 24-hour dose interval (AUC0-24) or for infinite time (AUC0-∞) | Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points. | 
| Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) | PK parameters of venetoclax will be described in cerebral spinal fluid including: oral clearance (CL/F) | Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric Relapsed/Refractory AML, Venetoclax, Pediatric AML