Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06131801

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancy Leukemia Lymphoma Acute Lymphocytic Leukemia ALL Acute Myelogenous Leukemia AML Chronic Myelogenous Leukemia CML Myeloproliferative Neoplasm Non Hodgkin Lymphoma Hodgkin Lymphoma Diffuse Large B Cell Lymphoma Follicular Lymphoma Burkitt Lymphoma T-cell Lymphoma B Cell Lymphoma Peripheral T Cell Lymphoma Cutaneous B-Cell Lymphoma	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.

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Children and Young Adults 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. Participants will receive Venetoclax as prescribed by their treating provider as part of their clinical care.

Arm

Intervention/Treatment

Children and Young Adults

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.

Participants will receive Venetoclax as prescribed by their treating provider as part of their clinical care.

Outcome Measures

Primary Outcome Measures

Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [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.]
PK parameters of venetoclax will be described in peripheral blood including: the observed peak plasma concentration (Cmax)
Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [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.]
PK parameters of venetoclax will be described in peripheral blood including: the time to peak (Tmax)
Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [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.]
PK parameters of venetoclax will be described in peripheral blood including: the apparent terminal phase elimination rate constant (β)
Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [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.]
PK parameters of venetoclax will be described in peripheral blood including: the terminal-phase elimination half-life (T1/2)
Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [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.]
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-∞)
Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [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.]
PK parameters of venetoclax will be described in peripheral blood including: oral clearance (CL/F) of venetoclax
Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
PK parameters of venetoclax will be described in cerebral spinal fluid including: the observed peak plasma concentration (Cmax)
Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
PK parameters of venetoclax will be described in cerebral spinal fluid including: the time to peak (Tmax)
Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
PK parameters of venetoclax will be described in cerebral spinal fluid including: the apparent terminal phase elimination rate constant (β)
Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
PK parameters of venetoclax will be described in cerebral spinal fluid including: the terminal-phase elimination half-life (T1/2)
Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
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-∞)
Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
PK parameters of venetoclax will be described in cerebral spinal fluid including: oral clearance (CL/F)

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 38 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.