Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06131801
• Other study ID #: Venetoclax PK
• Status: Recruiting
• Start date: November 15, 2023
• Est. completion date: December 1, 2027

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Site Public Contact
• Phone: (513) 636-2799
• Email: cancer[@]cchmc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 1, 2027
• Est. primary completion date: December 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 38 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Acute Myelogenous Leukemia
• ALL
• AML
• B Cell Lymphoma
• Burkitt Lymphoma
• Chronic Myelogenous Leukemia
• CML
• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• Hematologic Malignancy
• Hematologic Neoplasms
• Hodgkin Lymphoma
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms
• Non Hodgkin Lymphoma
• Peripheral T Cell Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Lymphoma

Intervention

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.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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 (ß)	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.
Primary	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.
Primary	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 (AUC0-8)	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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 (ß)	Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
Primary	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.
Primary	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 (AUC0-8)	Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
Primary	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.